Ashley Acheson

L-Tryptophan: Basic Metabolic Functions, Behavioral Research and Therapeutic Indications:

An essential component of the human diet, L-tryptophan is critical in a number of metabolic functions and has been widely used in numerous research and clinical trials. This review provides a brief overview of the role of L-tryptophan in protein synthesis and a number of other metabolic functions. With emphasis on L-tryptophans role in synthesis of brain serotonin, details are provided on the research uses of L-tryptophan, particularly L-tryptophan depletion, and on clinical trials that have been conducted using L-tryptophan supplementation. The ability to change the rates of serotonin synthesis in the brain by manipulating concentrations of serum tryptophan is the foundation of much research. As the sole precursor of serotonin, experimental research has shown that L-tryptophans role in brain serotonin synthesis is an important factor involved in mood, behavior, and cognition. Furthermore, clinical trials have provided some initial evidence of L-tryptophans efficacy for treatment of psychiatric disorders, particularly when used in combination with other therapeutic agents.

Effects of sleep deprivation on impulsive behaviors in men and women

The purpose of this study was to examine the effects of sleep deprivation on impulsive behavior. Patients with impulse control disorders often report sleep problems, and sleep deprivation even in healthy individuals impairs cognition, decision-making, and perhaps impulse control. To characterize the effects of sleep loss on specific forms of impulsive behavior, we tested the effects of overnight, monitored sleep deprivation on measures of impulsivity and cognition in healthy volunteers. Ten men and ten women completed two 24 h sessions in random order, in which they were either allowed to sleep normally or remained awake all night. At 8:30 am and 6:15 pm on the day after sleep or no sleep, participants were tested on the Balloon Analogue Risk Task (BART), the Experiential Discounting Task, the Adjusting Amount Delay and Probability Discounting Task, and the Stop Task. Participants also completed mood questionnaires and the Automated Neuropsychological Assessment Matrix (ANAM) throughout the course of the day. Sleep deprivation did not affect most of the measures of impulsive behavior. However, on the BART, sleep deprivation decreased risk taking in women, but not men. Sleep deprivation produced expected increases in subjective fatigue, and impaired performance on measures of attention and cognitive efficiency on the ANAM. The results indicate that sleep deprivation does not specifically increase impulsive behaviors but may differentially affect risk taking in men and women.

Impulsivity, attention, memory, and decision-making among adolescent marijuana users

RationaleMarijuana is a popular drug of abuse among adolescents, and they may be uniquely vulnerable to resulting cognitive and behavioral impairments. Previous studies have found impairments among adolescent marijuana users. However, the majority of this research has examined measures individually rather than multiple domains in a single cohesive analysis. This study used a logistic regression model that combines performance on a range of tasks to identify which measures were most altered among adolescent marijuana users.ObjectivesThe purpose of this research was to determine unique associations between adolescent marijuana use and performances on multiple cognitive and behavioral domains (attention, memory, decision-making, and impulsivity) in 14- to 17-year-olds while simultaneously controlling for performances across the measures to determine which measures most strongly distinguish marijuana users from nonusers.MethodsMarijuana-using adolescents (n = 45) and controls (n = 48) were tested. Logistic regression analyses were conducted to test for: (1) differences between marijuana users and nonusers on each measure, (2) associations between marijuana use and each measure after controlling for the other measures, and (3) the degree to which (1) and (2) together elucidated differences among marijuana users and nonusers.ResultsOf all the cognitive and behavioral domains tested, impaired short-term recall memory and consequence sensitivity impulsivity were associated with marijuana use after controlling for performances across all measures.ConclusionsThis study extends previous findings by identifying cognitive and behavioral impairments most strongly associated with adolescent marijuana users. These specific deficits are potential targets of intervention for this at-risk population.

Nucleus accumbens lesions decrease sensitivity to rapid changes in the delay to reinforcement

Both humans and non-humans discount the value of rewards that are delayed or uncertain, and individuals that discount delayed rewards at a relatively high rate are considered impulsive. To investigate the neural mechanisms that mediate delay discounting, the present study examined the effects of excitotoxic lesions of the nucleus accumbens (NAC) on discounting of reward value by delay and probability. Rats were trained on delay (n=24) or probability discounting (n=24) tasks. Following training, excitotoxic lesions of the NAC were made by intracranial injections of 0.5 microl 0.15 M quinolinic acid (n=12) or vehicle (n=12) aimed at the NAC (AP +1.6, ML +/-1.5, DV -7.1). NAC lesions did not alter performance in animals tested with a constant delay (4s) or probability (0.4) of reinforcement. However, when tested with between session changes in the delay (0, 1, 2, 4, and 8s) of reinforcement, the lesioned rats had flatter discount curves than the sham group, indicating that they were less sensitive to frequent changes in the delay to reward. In contrast, the NAC lesions did not affect discounting of probabilistic rewards. NAC lesions impaired the ability to adapt to frequent between session changes in the delay to reward but did not increase or decrease discounting when the delay was held constant across sessions. NAC lesions may disrupt the ability of the animals to predict the timing of delayed rewards when the delay to reward is changed frequently.

Prenatal alcohol exposure causes attention deficits in male rats

Children with fetal alcohol spectrum disorder (FASD) are often diagnosed with attention-deficit/ hyperactivity disorder (ADHD). These children show increases in reaction time (RT) variability and false alarms on choice reaction time (CRT) tasks. In this study, adult rats prenatally exposed to ethanol were trained to perform a CRT task. An analysis of the distribution of RTs obtained from the CRT task found that rats with a history of prenatal ethanol exposure had more variable RT distributions, possibly because of lapses of attention. In addition, it was found that, similar to children with FASD, the ethanol-exposed rats had more false alarms. Thus, rats with prenatal ethanol exposure show attention deficits that are similar to those of children with FASD and ADHD.

Bupropion improves attention but does not affect impulsive behavior in healthy young adults

Bupropion is an effective abstinence aid for cessation of smoking and possibly other drug use as well. There is evidence that bupropion improves attention and impulse control in certain patient populations, and improvements in these processes could mediate its efficacy as an abstinence aid. In the present study, we tested the effects of acute bupropion on measures of attention and impulsivity in healthy adults with d-amphetamine included as a positive control. Twenty-two nonsmokers (11 women) and 11 smokers (4 women) completed four 4-hr sessions where they received placebo, bupropion (150 or 300 mg), or d-amphetamine (20 mg) in capsules. Ninety minutes after capsule administration, participants were tested on attention with a simple reaction time task (SRT) and on impulsivity with the stop task, a delay and probability discounting task (DPD), and the balloon analogue risk task (BART). Participants also completed mood questionnaires during sessions. Bupropion (150 mg) decreased lapses in attention on the SRT, but did not affect performance on the stop task, DPD, or BART. Amphetamine decreased lapses in attention and speeded sensory motor processing time on the SRT but did not significantly affect responding on the stop task or DPD. On the BART, d-amphetamine tended to decrease risk taking in men but increased risk taking in women. Bupropion (300 mg) and d-amphetamine increased ratings of arousal. These results suggest that bupropion improves attention without affecting impulsive behavior in healthy adults. Improvements in attention may contribute to the effectiveness of bupropion as a pharmacotherapy for smoking.

Differential activation of the anterior cingulate cortex and caudate nucleus during a gambling simulation in persons with a family history of alcoholism: Studies from the Oklahoma Family Health Patterns Project

Individuals with a family history of alcoholism (FH+) are at enhanced risk of developing an alcohol or other substance use disorder relative to those without this history (FH-). Recent studies comparing FH+ and FH- individuals have revealed differences in cognition, emotion processing, sociability, and decision-making. These differences suggest possible altered brain functioning in FH+ individuals that may play a crucial role in vulnerability to substance use disorders. In the present study, 15 FH+ and 19 FH- individuals performed the Iowa Gambling Task (IGT), a simulated card game requiring integration of payoff-to-penalty ratios, while undergoing functional magnetic resonance imaging. All participants performed the task more conservatively as the session progressed, and the FH groups achieved similar payoffs by the end of the game. Imaging revealed a distributed network of brain regions that was engaged when subjects performed this task, including the right inferior frontal and postcentral gyri, left parahippocampal gyrus, insula and precuneous cortices, left inferior and superior parietal lobules, left lentiform nucleus and bilateral culmen, claustrum, lingual gyri and cerebellar tonsils. Despite a lack of behavioral differences between groups, the FH+ participants showed significantly more activation in the left dorsal anterior cingulate cortex and left caudate nucleus. These findings correspond to models of risk in FH+ persons that postulate biases in brain decision-making systems as underlying elevated risk for alcoholism.

Greater Discounting of Delayed Rewards in Young Adults with Family Histories of Alcohol and Drug Use Disorders: Studies from the Oklahoma Family Health Patterns Project

BACKGROUND Increased discounting of delayed rewards may be a premorbid characteristic and possible risk factor for alcohol and other drug use disorders; however, previous studies have found no or minimal differences in delay discounting in individuals at risk for substance use disorders based on family history. It is possible that increased delay discounting may be more closely associated with antisocial traits, evident in a subset of individuals with positive family histories of alcohol and drug use disorders, and that previous studies were underpowered for detecting subtle to modest overall group differences. METHODS In this study, we compared 143 young adults with family histories of alcohol and other drug use disorders (FH+) and 155 young adults with no such histories (FH-) on delay discounting and subsequently examined how delay discounting was related to antisocial traits and other selected psychological and demographic variables. RESULTS The FH+ group discounted delayed rewards more than the FH- group. Subsequent analyses revealed that increased delay discounting was correlated with having more parents and grandparents with alcohol and drug use disorders, more antisocial traits, more depressive tendencies and lower IQs, and lower income. After controlling for all these relationships, more antisocial traits and lower IQ still predicted greater delay discounting, and subsequent analysis revealed that the greater delay discounting in the FH+ group was mediated by this groups greater number of individuals with antisocial traits. CONCLUSION FH+ individuals who discount delayed rewards more may be at increased risk for developing alcohol and other drug use disorders; however, additional descriptive studies and longitudinal studies are needed.

Adults with a family history of alcohol related problems are more impulsive on measures of response initiation and response inhibition

BACKGROUND Previous studies have found individuals with family histories of alcohol use disorders are more impulsive on some but not all laboratory behavioral measures, suggesting deficits on specific forms of impulse control. However, drawing conclusions is tenuous because these different measures have not been administered together in the same group of participants. METHODS In the present study, we compared healthy 21-35 year old adults with family histories of alcohol related problems (FHAP+) or without such histories (FHAP-) on behavioral measures of response inhibition, response initiation, and consequence sensitivity impulsivity. FHAP+ (n=36) and FHAP- (n=36) participants were compared on performance on the Immediate Memory Task (IMT, response initiation), GoStop Impulsivity Paradigm (GoStop, response inhibition), Two Choice Impulsivity Paradigm (TCIP, consequence sensitivity) and Single Key Impulsivity Paradigm (SKIP, consequence sensitivity). RESULTS FHAP+ individuals were more impulsive on the IMT and GoStop but not on the TCIP or SKIP. CONCLUSIONS These results suggest that response initiation and response inhibition impulsivity are increased in individuals with family histories of alcohol related problems despite not having alcohol or drug use disorders themselves. In contrast, increased consequence sensitivity impulsivity may be associated with additional risk factors such as more severe family histories of alcohol use disorders, or it may be increased as a consequence of heavy drug or alcohol use.

Comparing the Detection of Transdermal and Breath Alcohol Concentrations During Periods of Alcohol Consumption Ranging From Moderate Drinking to Binge Drinking

Binge drinking is a public health concern due to its association with negative health outcomes as well as increased legal and social consequences. Previous studies have frequently used self-reported alcohol consumption to classify binge drinking episodes; however, these measures are often limited in both detail and accuracy. Some researchers have begun using additional measures such as blood (BAC) and breath (BrAC) alcohol concentrations to supplement self-report data. Transdermal alcohol testing, or the detection of alcohol expiration through the skin, offers advantages over BAC and BrAC measures by allowing for continuous and noninvasive monitoring of an individuals drinking behavior in real time. Despite these advantages, this technology has not been widely used or studied outside of forensic applications. The present research compares transdermal alcohol concentration (TAC) and BrAC readings during the consumption of alcohol ranging from moderate drinking to binge drinking in 22 adult regular drinkers in order to investigate the sensitivity and specificity of the TAC monitors. We observed that BrAC and TAC measures were broadly consistent. Additionally, we were able to develop an equation that could predict BrAC results using TAC data, indicating TAC data would be an appropriate substitute in research and clinical contexts where BrAC readings are typically used. Finally, we were able to determine a cutoff point for peak TAC data that could reliably predict whether a participant had engaged in moderate or more-than-moderate drinking, suggesting TAC monitors could be used in settings where moderate or reduced drinking is the goal.