ABSTRACT
Deaf patients who communicate in American Sign Language (ASL) experience communication challenges leading to medical errors, treatment delays, and health disparities. Research on Deaf patient communication preferences is sparse. Researchers conducted focus groups based on the Health Belief Model with culturally Deaf patients and interpreters. The ASL focus groups were interpreted and transcribed into written English, verified by a third-party interpreting agency, and uploaded into NVivo. Deductive coding was used to identify communication methods and inductive coding was used to identify themes within each. Writing back-and-forth introduced challenges related to English proficiency, medical terminology, poor penmanship, and tendencies of providers to abbreviate. Participants had various speechreading abilities and described challenges with mask mandates. Multiple issues were identified with family and friends as proxy interpreters, including a lack of training, confidentiality issues, emotional support, and patient autonomy. Video remote interpreter challenges included technical, environmental, and interpreter qualification concerns. Participants overwhelmingly preferred on-site interpreters for communication clarity. While there was a preference for direct care, many acknowledged this is not always feasible due to lack of providers fluent in ASL. Access to on-site interpreters is vital for many Deaf patients to provide full access to critical medical information. BudgetĀ allocation for on-call interpreters is important in emergency settings.
Subject(s)
Deafness , Humans , Communication , Sign Language , Focus Groups , Health Personnel , Communication Barriers , TranslatingABSTRACT
Pseudo-hyponatremia is an uncommon laboratory finding that can lead to serious morbidity and mortality if not recognized abruptly. Often linked to conditions like hyperlipidemia or hyperproteinemia, pseudohyponatremia can mislead clinicians and result in misdiagnosis. We discuss this through two real-world case studies, explaining how it develops and how to diagnose it accurately. It's paramount that clinicians recognize and properly differentiate pseudohyponatremia from true hyponatremia to prevent wrong treatments. We stress the need to address the root causes in order to provide the optimal patient care.
ABSTRACT
EXECUTIVE SUMMARY: Winds of change have been blowing in the U.S. healthcare system since passage of the Affordable Care Act. Examining differences between individuals covered by different types of insurance is essential if healthcare executives are to develop new strategies in response to the emerging health insurance market. In this study, we used multigroup path analysis models to examine the moderating effects of health insurance on direct and indirect associations with general health status, satisfaction with received care, financial burden, and perceived value of the healthcare system. Data were obtained from the 2012 Medical Expenditure Panel Survey and analyzed according to the types of insurance: private, public, and military. With the satisfactory fit of the model (χ = 2,532.644, df = 96, p < .001; normed fit index = 0.943; incremental fit index = 0.945; comparative fit index = 0.957; root mean squared error of approximation = 0.044), higher healthcare quality was positively associated with better health status, greater satisfaction, and greater perceived value of the healthcare system in the three insurance groups. In addition, although all direct paths between health service quality and financial burden were not statistically significant, indirect effects were significant in all models through health status. Being married and earning higher incomes were also found to be strong predictors of better health status and health service quality. Efforts to improve the quality of health services are needed, which could contribute to a reduction in health disparities among insurance beneficiaries and result in less healthcare spending.
Subject(s)
Health Expenditures , Income , Insurance, Health , Patient Protection and Affordable Care Act , Humans , Insurance Coverage , Quality of Health Care , United StatesABSTRACT
BACKGROUND: Individuals with substance use disorders typically exhibit a predilection toward instant gratification with apparent disregard for the future consequences of their actions. Indirect evidence suggests that low dopamine D2-type receptor availability in the striatum contributes to the propensity of these individuals to sacrifice long-term goals for short-term gain; however, this possibility has not been tested directly. We investigated whether striatal D2/D3 receptor availability is negatively correlated with the preference for smaller, more immediate rewards over larger, delayed alternatives among research participants who met DSM-IV criteria for methamphetamine (MA) dependence. METHODS: Fifty-four adults (n = 27 each: MA-dependent, non-user controls) completed the Kirby Monetary Choice Questionnaire, and underwent positron emission tomography scanning with [(18)F]fallypride. RESULTS: MA users displayed steeper temporal discounting (p = 0.030) and lower striatal D2/D3 receptor availability (p < 0.0005) than controls. Discount rate was negatively correlated with striatal D2/D3 receptor availability, with the relationship reaching statistical significance in the combined sample (r = -0.291, p = 0.016) and among MA users alone (r = -0.342, p = 0.041), but not among controls alone (r = -0.179, p = 0.185); the slopes did not differ significantly between MA users and controls (p = 0.5). CONCLUSIONS: These results provide the first direct evidence of a link between deficient D2/D3 receptor availability and steep temporal discounting. This finding fits with reports that low striatal D2/D3 receptor availability is associated with a higher risk of relapse among stimulant users, and may help to explain why some individuals choose to continue using drugs despite knowledge of their eventual negative consequences. Future research directions and therapeutic implications are discussed.
Subject(s)
Amphetamine-Related Disorders/metabolism , Corpus Striatum/metabolism , Methamphetamine/toxicity , Positron-Emission Tomography , Receptors, Dopamine D2/metabolism , Receptors, Dopamine D3/metabolism , Reward , Adult , Amphetamine-Related Disorders/diagnostic imaging , Benzamides/administration & dosage , Central Nervous System Stimulants/toxicity , Corpus Striatum/diagnostic imaging , Diagnostic and Statistical Manual of Mental Disorders , Dopamine/metabolism , Female , Fluorine Radioisotopes/administration & dosage , Humans , Male , Middle Aged , Surveys and Questionnaires , Young AdultABSTRACT
Moderate doses of stimulant drugs are known to enhance memory encoding and consolidation, but their effects on memory retrieval have not been explored in depth. In laboratory animals, stimulants seem to improve retrieval of emotional memories, but comparable studies have not been carried out in humans. In the present study, we examined the effects of dextroamphetamine (AMP) on retrieval of emotional and unemotional stimuli in healthy young adults, using doses that enhanced memory formation when administered before encoding in our previous study. During 3 sessions, healthy volunteers (n = 31) received 2 doses of AMP (10 and 20 mg) and placebo in counterbalanced order under double-blind conditions. During each session, they first viewed emotional and unemotional pictures and words in a drug-free state, and then 2 days later their memory was tested, 1 hour after AMP or placebo administration. Dextroamphetamine did not affect the number of emotional or unemotional stimuli remembered, but both doses increased recall intrusions and false recognition. Dextroamphetamine (20 mg) also increased the number of positively rated picture descriptions and words generated during free recall. These data provide the first evidence that therapeutic range doses of stimulant drugs can increase memory retrieval errors. The ability of AMP to positively bias recollection of prior events could contribute to its potential for abuse.
Subject(s)
Central Nervous System Stimulants/adverse effects , Dextroamphetamine/adverse effects , Memory Disorders/chemically induced , Memory, Episodic , Mental Recall/drug effects , Adult , Double-Blind Method , Emotions , Female , Healthy Volunteers , Humans , Male , Memory Disorders/diagnosis , Memory Disorders/psychology , Photic Stimulation , Time Factors , Young AdultABSTRACT
BACKGROUND: Surgical site infections (SSI) associated with elective pediatric spinal surgery are a commonly reported complication, increasing hospital length of stay, readmissions, operations, and financial costs. In July 2007, a multidisciplinary task force, designated Target Zero, was created to address this issue and establish prevention protocols at our institution. METHODS: A consecutive series of 394 patient charts from April 2006 to September 2008 were retrospectively reviewed to identify patients who developed an SSI secondary to elective spinal surgery. Four cohorts were evaluated; high-risk (HR) and low-risk (LR) patients who underwent surgery before (April 2006 to June 2007) and after (July 2007 to September 2008) Target Zero initiation. The definition of HR included diagnoses of cerebral palsy, spina bifida, muscle disease, paralytic deformities, and vertebral column resections. Patients were followed for 1 year to meet The Center for Disease Control-National Health Safety Network's definition of an SSI with an implantable device. Overall infection rates were determined for each group and compared statistically. RESULTS: A total of 192 patients (70 HR and 122 LR) underwent surgery before, and 202 patients (92 HR and 110 LR) underwent surgery after Target Zero initiation. Overall infection rates were reduced from 7.8% to 4.5% (P=0.203), 12.9% to 6.5% (P=0.183), and 4.9% to 2.7% (P=0.505) for all patients, HR patients, and LR patients, respectively. The relative risk reduction was 43.0% for all patients, 49.3% for HR patients, and 44.6% for LR patients. CONCLUSIONS: Although decreases in overall infection rates were not statistically significant, the results from Target Zero were shown to be clinically meaningful with a relative risk reduction approaching 50% overall and in defined subgroups. Based on the number needed to treat analysis, 1 infection in every 16 patients within the HR group, and 1 in 30 overall, was prevented up to 1 year postoperatively. This study is the first to document the effectiveness of a multidisciplinary team implementing protocols for decreasing infection rates in pediatric spine surgery.
Subject(s)
Orthopedic Procedures/methods , Patient Care Team/organization & administration , Spinal Diseases/surgery , Surgical Wound Infection/prevention & control , Child , Elective Surgical Procedures/adverse effects , Elective Surgical Procedures/methods , Follow-Up Studies , Humans , Length of Stay , Orthopedic Procedures/adverse effects , Retrospective Studies , Risk Factors , Spinal Diseases/physiopathology , Surgical Wound Infection/epidemiologyABSTRACT
Post-traumatic stress disorder (PTSD) leads to impairments in both cognitive and affective functioning. Animal work suggests that chronic stress reduces dopamine tone, and both animal and human studies argue that changes in dopamine tone influence working memory, a core executive function. These findings give rise to the hypothesis that increasing cortical dopamine tone in individuals with greater PTSD symptomatology should improve working memory performance. In this pharmacological functional magnetic resonance imaging (fMRI) study, 30 US military veterans exhibiting a range of PTSD severity completed an emotional working memory task. Each subject received both placebo and the catechol-O-methyl transferase inhibitor tolcapone, which increases cortical dopamine tone, in randomized, double-blind, counterbalanced fashion. Mnemonic discriminability (calculated with d', an index of the detectability of working memory signals) and response bias were evaluated in the context of task-related brain activations. Subjects with more severe PTSD showed both greater tolcapone-mediated improvements in d' and larger tolcapone-mediated reductions in liberally-biased responding for fearful stimuli. FMRI revealed that tolcapone augmented activity within bilateral frontoparietal control regions during the decision phase of the task. Specifically, tolcapone increased cortical responses to fearful relative to neutral stimuli in higher severity PTSD subjects, and reduced cortical responses to fearful stimuli for lower severity PTSD subjects. Moreover, tolcapone modulated prefrontal connectivity with areas overlapping the default mode network. These findings suggest that enhancing cortical dopamine tone may represent an approach to remediating cognitive and affective dysfunction in individuals with more severe PTSD symptoms.
Subject(s)
Dopamine , Stress Disorders, Post-Traumatic , Brain/metabolism , Catechol O-Methyltransferase/metabolism , Catechol O-Methyltransferase Inhibitors , Humans , Magnetic Resonance Imaging , Memory, Short-Term , Stress Disorders, Post-Traumatic/diagnostic imaging , Stress Disorders, Post-Traumatic/drug therapyABSTRACT
STUDY OBJECTIVES: The development of ambulatory technologies capable of monitoring brain activity during sleep longitudinally is critical for advancing sleep science. The aim of this study was to assess the signal acquisition and the performance of the automatic sleep staging algorithms of a reduced-montage dry-electroencephalographic (EEG) device (Dreem headband, DH) compared to the gold-standard polysomnography (PSG) scored by five sleep experts. METHODS: A total of 25 subjects who completed an overnight sleep study at a sleep center while wearing both a PSG and the DH simultaneously have been included in the analysis. We assessed (1) similarity of measured EEG brain waves between the DH and the PSG; (2) the heart rate, breathing frequency, and respiration rate variability (RRV) agreement between the DH and the PSG; and (3) the performance of the DH's automatic sleep staging according to American Academy of Sleep Medicine guidelines versus PSG sleep experts manual scoring. RESULTS: The mean percentage error between the EEG signals acquired by the DH and those from the PSG for the monitoring of α was 15 Ā± 3.5%, 16 Ā± 4.3% for Ć, 16 Ā± 6.1% for λ, and 10 Ā± 1.4% for ĆĀø frequencies during sleep. The mean absolute error for heart rate, breathing frequency, and RRV was 1.2 Ā± 0.5 bpm, 0.3 Ā± 0.2 cpm, and 3.2 Ā± 0.6%, respectively. Automatic sleep staging reached an overall accuracy of 83.5 Ā± 6.4% (F1 score: 83.8 Ā± 6.3) for the DH to be compared with an average of 86.4 Ā± 8.0% (F1 score: 86.3 Ā± 7.4) for the 5 sleep experts. CONCLUSIONS: These results demonstrate the capacity of the DH to both monitor sleep-related physiological signals and process them accurately into sleep stages. This device paves the way for, large-scale, longitudinal sleep studies. CLINICAL TRIAL REGISTRATION: NCT03725943.
Subject(s)
Electroencephalography , Sleep Stages , Algorithms , Polysomnography , SleepSubject(s)
Bias, Implicit , Physicians , Pregnancy , Humans , Female , Maternal Mortality , Reproductive Health , ParturitionABSTRACT
Individuals with drug use disorders seek drugs over other rewarding activities, and exhibit neurochemical deficits related to dopamine, which is involved in value-based learning and decision-making. Thus, a dopaminergic disturbance may underpin drug-biased choice in addiction. Classical drug-choice assessments, which offer drug-consumption opportunities, are inappropriate for addicted individuals seeking treatment or abstaining. Fifteen recently abstinent methamphetamine users and 15 healthy controls completed two laboratory paradigms of 'simulated' drug choice (choice for drug-related vs affectively pleasant, unpleasant, and neutral images), and underwent positron emission tomography measurements of dopamine D2-type receptor availability, indicated by binding potential (BPND) for [18F]fallypride. Thirteen of the methamphetamine users and 10 controls also underwent [11C]NNC112 PET scans to measure dopamine D1-type receptor availability. Group analyses showed that, compared with controls, methamphetamine users chose to view more methamphetamine-related images on one task, with a similar trend on the second task. Regression analyses showed that, on both tasks, the more methamphetamine users chose to view methamphetamine images, specifically vs pleasant images (the most frequently chosen images across all participants), the lower was their D2-type BPND in the lateral orbitofrontal cortex, an important region in value-based choice. No associations were observed with D2-type BPND in striatal regions, or with D1-type BPND in any region. These results identify a neurochemical correlate for a laboratory drug-seeking paradigm that can be administered to treatment-seeking and abstaining drug-addicted individuals. More broadly, these results refine the central hypothesis that dopamine-system deficits contribute to drug-biased decision-making in addiction, here showing a role for the orbitofrontal cortex.
Subject(s)
Amphetamine-Related Disorders/metabolism , Choice Behavior/physiology , Corpus Striatum/metabolism , Methamphetamine/adverse effects , Prefrontal Cortex/metabolism , Receptors, Dopamine D2/metabolism , Adult , Amphetamine-Related Disorders/diagnostic imaging , Corpus Striatum/diagnostic imaging , Drug-Seeking Behavior/physiology , Female , Humans , Male , Middle Aged , Photic Stimulation/methods , Positron-Emission Tomography/methods , Prefrontal Cortex/diagnostic imaging , Psychomotor Performance/physiology , RewardABSTRACT
RATIONALE: Neuroleptic dysphoria encompasses a range of unpleasant subjective responses and, as a result, is difficult to study in preclinical animal models. OBJECTIVE: Based on the learned helplessness model of depression, increases in escape failures (EFs) in the drug-induced helplessness test (DH) are proposed to reflect drug-induced depressive-like state, a contributing factor to neuroleptic dysphoria in humans. MATERIALS AND METHODS: Effects of the typical antipsychotic haloperidol and the atypical antipsychotics risperidone, olanzapine, aripiprazole, quetiapine, and clozapine were investigated in the DH test. We further characterized this test by examining compounds affecting motor function, cognition, anxiety, and those with antidepressant activity. RESULTS: The antipsychotics haloperidol, risperidone, aripiprazole, and olanzapine, all increased EFs, while quetiapine had no effect, and clozapine reduced EFs. Amphetamine, diazepam, and ciproxifan, had no effect on EFs. Scopolamine significantly reduced EFs and MK-801 showed a trend toward reducing EFs at doses not significantly sti mulating locomotor activity. Subchronic, but not acute, imipramine and subchronic fluoxetine significantly reduced EFs at doses significantly suppressing locomotor activity. Dissociation appears to exist between performance in the DH test and compound effects on catalepsy or locomotor activity. CONCLUSIONS: After discussing potential alternative interpretations of the drug-induced changes of EFs, we propose the DH test as a useful test for assessing a drug-induced, depressive-like state that may contribute to neuroleptic dysphoria.
Subject(s)
Affect/drug effects , Antidepressive Agents/pharmacology , Antipsychotic Agents/toxicity , Disease Models, Animal , Escape Reaction/drug effects , Helplessness, Learned , Motivation , Animals , Antipsychotic Agents/antagonists & inhibitors , Arousal/drug effects , Avoidance Learning/drug effects , Awareness/drug effects , Dose-Response Relationship, Drug , Humans , Male , Motor Activity/drug effects , Rats , Rats, Sprague-Dawley , Reaction Time/drug effectsABSTRACT
Rats treated with apomorphine and amphetamine display sensorimotor gating impairments, as measured by prepulse inhibition (PPI), and these impairments can be reversed by antipsychotic treatment. However, it remains unknown whether the dopamine (DA) D(3) receptor plays a role in mediating these effects on PPI, as none of these DA agonists or antipsychotics are exclusively selective at either D(2) or D(3) receptors. To address this question, the current study was designed to investigate whether antipsychotic drugs and selective D(3) antagonists could block the PPI-disruptive effects of PD 128907 (a preferential D(3) agonist) and apomorphine. We found that the effect of PD 128907 on PPI in rats could be antagonized by risperidone, clozapine, and the selective D(3) antagonists SB 277011 and A-691990, but not by raclopride or haloperidol, while the apomorphine-induced PPI deficit could be reversed by risperidone, clozapine and haloperidol, but not by SB 2770111 and A-691990. These results suggest that the D(3) receptor does not mediate apomorphine-induced disruption of PPI in rats, however, given the findings that PD 128907 elicited a PPI-disruptive effect that was blocked by selective D(3) antagonists, a role of D(3) receptor in mediating PPI in rats cannot be ruled out. The possible mechanisms of D(3) receptor involvement in PPI are discussed.
Subject(s)
Antipsychotic Agents/pharmacology , Apomorphine/pharmacology , Benzopyrans/pharmacology , Dopamine Agonists/pharmacology , Inhibition, Psychological , Oxazines/pharmacology , Reflex, Startle/drug effects , Acoustic Stimulation/methods , Analysis of Variance , Animals , Behavior, Animal/drug effects , Body Temperature/drug effects , Dopamine Antagonists/pharmacology , Dose-Response Relationship, Drug , Drug Interactions , Male , Nitriles/pharmacology , Rats , Rats, Wistar , Tetrahydroisoquinolines/pharmacologyABSTRACT
Schizophrenic patients typically exhibit impairment of sensorimotor gating, which can be modeled in animal models such as the test of prepulse inhibition of startle response (PPI) in rodents. It has been found that antipsychotics enhanced PPI in DBA mice and reversed the PPI deficit induced by neonatal ventral hippocampal (NVH) lesions in rats. However, the relative involvement of D(3) and D(2) receptors in these effects is unknown since all antipsychotics are D(2)/D(3) antagonists with limited binding preference at D(2) receptors. Therefore, in the current study, we investigated the influence of several dopamine antagonists with higher selectivity at D(3) vs D(2) receptors on PPI in DBA/2J mice and in NVH-lesioned rats. The PPI in DBA/2J mice was enhanced by the nonselective D(2)/D(3) antagonists, haloperidol at 0.3-3 mg/kg, or risperidone at 0.3-1 mg/kg, while PPI-enhancing effects were observed after the administration of higher doses of the preferential D(3)/D(2) antagonist, BP 897 at 8 mg/kg, and the selective D(3) antagonists, SB 277011 at 30 mg/kg and A-437203 at 30 mg/kg. No effect was observed following the treatment with the selective D(3) antagonist, AVE 5997 up to 30 mg/kg. The PPI deficits induced by NVH lesions were reversed by haloperidol but not by the more selective D(3) antagonists, A-437203 and AVE 5997. BP 897 enhanced PPI nonselectivity, that is, in both lesioned and nonlesioned rats. In summary, the present study indicates that PPI-enhancing effects induced by antipsychotics in DBA/2J mice and in NVH-lesioned rats are unlikely to be mediated by D(3) receptors.
Subject(s)
Dopamine Antagonists/pharmacology , Hippocampus/physiology , Neural Inhibition/drug effects , Receptors, Dopamine D3/antagonists & inhibitors , Reflex, Startle/drug effects , Analysis of Variance , Animals , Animals, Newborn , Behavior, Animal/drug effects , Dopamine Agonists/pharmacology , Dose-Response Relationship, Drug , Drug Interactions , Hippocampus/drug effects , Hippocampus/injuries , Ibotenic Acid/toxicity , Male , Mice , Mice, Inbred DBA , Piperazines/pharmacology , RatsABSTRACT
Since H3 receptor (H3R) antagonists/inverse agonists can improve cognitive function in animal models, they may have the potential to be used as add-on therapy in the treatment of schizophrenia, a disease with significant cognitive deficits. However, a recent study showed potentiation of haloperidol-induced catalepsy by ciproxifan, an imidazole-containing H3R antagonist/inverse agonist, suggesting there is a potential risk of exacerbating extrapyramidal symptoms (EPS) if H3R antagonists were used as adjunctive treatment [Pillot, C., Ortiz, J., Heron, A., Ridray, S., Schwartz, J.C. and Arrang, J.M., Ciproxifan, a histamine H3-receptor antagonist/inverse agonist, potentiates neurochemical and behavioral effects of haloperidol in the rat, J Neurosci, 22 (2002) 7272-80]. In order to clarify the basis of this finding, we replicated this result and extended the work with another imidazole and two non-imidazole H3R antagonists. The results indicate that ciproxifan significantly augmented the effects of haloperidol and risperidone on catalepsy. Another imidazole H3R antagonist, thioperamide, also potentiated the effect of risperidone on catalepsy. In contrast, no catalepsy-enhancing effects were observed when selective non-imidazole H3R antagonists, ABT-239 and A-431404, were coadministered with haloperidol and/or risperidone. As ciproxifan and thioperamide are inhibitors of cytochrome P450 enzymes, responsible for metabolizing risperidone and haloperidol, the possibility that the augmentation of antipsychotics by imidazoles resulted from drug-drug interactions was tested. A drug metabolism study revealed that an imidazole, but not a non-imidazole, potently inhibited the metabolism of haloperidol and risperidone. Furthermore, ketoconazole, an imidazole-based CYP 3A4 inhibitor, significantly augmented risperidone-induced catalepsy. Together, these data suggest the potentiation of antipsychotic-induced catalepsy may result from pharmacokinetic drug-drug interactions and support the potential utility of non-imidazole H3R antagonists in treatment of cognitive impairment in schizophrenia without increased risk of increased EPS in patients.
Subject(s)
Antipsychotic Agents/pharmacokinetics , Brain Chemistry/drug effects , Cataplexy/chemically induced , Histamine Antagonists/pharmacokinetics , Histamine/metabolism , Receptors, Histamine H3/drug effects , Animals , Antipsychotic Agents/adverse effects , Benzofurans/chemistry , Benzofurans/pharmacokinetics , Brain Chemistry/physiology , Cataplexy/physiopathology , Cataplexy/prevention & control , Cytochrome P-450 Enzyme System/drug effects , Cytochrome P-450 Enzyme System/metabolism , Drug Combinations , Drug Synergism , Haloperidol/pharmacokinetics , Histamine Antagonists/chemistry , Imidazoles/chemistry , Imidazoles/pharmacokinetics , Ketoconazole/pharmacokinetics , Male , Metabolic Clearance Rate/drug effects , Metabolic Clearance Rate/physiology , Piperidines/chemistry , Piperidines/pharmacokinetics , Pyrrolidines/chemistry , Pyrrolidines/pharmacokinetics , Rats , Rats, Sprague-Dawley , Receptors, Histamine H3/metabolism , Risperidone/pharmacokinetics , Schizophrenia/drug therapyABSTRACT
Despite aggressive efforts to contain it, methamphetamine use disorder continues to be major public health problem; and with generic behavioral therapies still the mainstay of treatment for methamphetamine abuse, rates of attrition and relapse remain high. This review summarizes the findings of structural, molecular, and functional neuroimaging studies of methamphetamine abusers, focusing on cortical and striatal abnormalities and their potential contributions to cognitive and behavioral phenotypes that can serve to promote compulsive drug use. These studies indicate that individuals with a history of chronic methamphetamine abuse often display several signs of corticostriatal dysfunction, including abnormal gray- and white-matter integrity, monoamine neurotransmitter system deficiencies, neuroinflammation, poor neuronal integrity, and aberrant patterns of brain connectivity and function, both when engaged in cognitive tasks and at rest. More importantly, many of these neural abnormalities were found to be linked with certain addiction-related phenotypes that may influence treatment response (e.g., poor self-control, cognitive inflexibility, maladaptive decision-making), raising the possibility that they may represent novel therapeutic targets.
Subject(s)
Amphetamine-Related Disorders/pathology , Amphetamine-Related Disorders/physiopathology , Brain/drug effects , Central Nervous System Stimulants/administration & dosage , Methamphetamine/administration & dosage , Amphetamine-Related Disorders/psychology , Amphetamine-Related Disorders/therapy , Animals , Brain/pathology , Brain/physiopathology , Humans , NeuroimagingABSTRACT
Understanding how stimulant drugs affect memory is important for understanding their addictive potential. Here we examined the effects of acute d-methamphetamine (METH), administered either before (encoding phase) or immediately after (consolidation phase) study on memory for emotional and neutral images in healthy humans. Young adult volunteers (N = 60) were randomly assigned to either an encoding group (N = 29) or a consolidation group (N = 31). Across three experimental sessions, they received placebo and two doses of METH (10, 20 mg) either 45 min before (encoding) or immediately after (consolidation) viewing pictures of emotionally positive, neutral, and negative scenes. Memory for the pictures was tested two days later, under drug-free conditions. Half of the sample reported sleep disturbances following the high dose of METH, which affected their memory performance. Therefore, participants were classified as poor sleepers (less than 6 hours; n = 29) or adequate sleepers (6 or more hours; n = 31) prior to analyses. For adequate sleepers, METH (20 mg) administered before encoding significantly improved memory accuracy relative to placebo, especially for emotional (positive and negative), compared to neutral, stimuli. For poor sleepers in the encoding group, METH impaired memory. METH did not affect memory in the consolidation group regardless of sleep quality. These results extend previous findings showing that METH can enhance memory for salient emotional stimuli but only if it is present at the time of study, where it can affect both encoding and consolidation. METH does not appear to facilitate consolidation if administered after encoding. The study also demonstrates the important role of sleep in memory studies.
Subject(s)
Central Nervous System Stimulants/pharmacology , Emotions/drug effects , Memory/drug effects , Methamphetamine/pharmacology , Administration, Oral , Adolescent , Adult , Central Nervous System Stimulants/administration & dosage , Female , Healthy Volunteers , Humans , Male , Methamphetamine/administration & dosage , Random Allocation , Recognition, Psychology/drug effects , Surveys and Questionnaires , Young AdultABSTRACT
BACKGROUND: Dopamine D2/D3 receptor availability in the striatum has been linked with executive function in healthy individuals, and is below control levels among drug addicts, possibly contributing to diminished executive function in the latter group. This study tested for an association of striatal D2/D3 receptor availability with a measure of executive function among research participants who met DSM-IV criteria for methamphetamine dependence. METHODS: Methamphetamine users and non-user controls (n = 18 per group) completed the Wisconsin Card Sorting Test and positron emission tomography with [18F]fallypride. RESULTS: The methamphetamine users displayed significantly lower striatal D2/D3 receptor availability on average than controls after controlling for age and education (p = 0.008), but they did not register greater proportions of either perseverative or non-perseverative errors when controlling for education (both ps ≥ 0.622). The proportion of non-perseverative, but not perseverative, errors was negatively correlated with striatal D2/D3 receptor availability among controls (r = -0.588, p = 0.010), but not methamphetamine users (r = 0.281, p = 0.258), and the group-wise interaction was significant (p = 0.030). CONCLUSIONS: These results suggest that cognitive flexibility, as measured by perseverative errors on the Wisconsin Card Sorting Test, is not determined by signaling through striatal D2/D3 receptors in healthy controls, and that in stimulant abusers, who have lower D2/D3 receptor availability, compensation can effectively maintain other executive functions, which are associated with D2/D3 receptor signaling in controls.
Subject(s)
Amphetamine-Related Disorders/metabolism , Executive Function/physiology , Methamphetamine/adverse effects , Receptors, Dopamine D2/metabolism , Receptors, Dopamine D3/metabolism , Substance-Related Disorders/metabolism , Adult , Case-Control Studies , Corpus Striatum/metabolism , Executive Function/drug effects , Female , Humans , Male , Middle Aged , Neuropsychological Tests , Positron-Emission Tomography/methodsABSTRACT
RATIONALE: The rat neonatal ventral hippocampal (VH) ibotenic lesion model has been proposed as a developmental model of schizophrenia, based on evidence that it encompasses aspects of the disorder including psychomotor agitation (hyperactivity), deficits in prepulse inhibition (PPI), and deficits in social interaction (SI), measures presumed to reflect positive symptoms, sensory gating deficits and negative symptoms, respectively. However, validation of the model as a predictive pharmacological screening tool has been minimal. OBJECTIVE: Determine the effects of a chronic 3-week low dose treatment of clozapine or risperidone on locomotor hyperactivity, PPI and SI in lesioned and control rats. RESULTS: Both clozapine, 2.5 mg/kg per day IP and risperidone, 0.1 mg/kg per day IP, reversed lesion-induced locomotor hyperactivity; however, the compounds also decreased locomotor activity in the non-lesioned controls. Clozapine 2.5 mg/kg per day and risperidone 0.1 mg/kg per day significantly attenuated lesion-induced PPI deficits. Neither compound induced a significant attenuation of lesion-induced SI deficits. In order to see if SI deficits required a higher dose of an antipsychotic, the dose of clozapine was increased to 4 mg/kg per day; however this dose induced such marked decreases in the activity and startle responses in the control rats, i.e. up to 74% decrease, that the effects on the lesioned rats could not be adequately interpreted. CONCLUSIONS: These data add further support to the neonatal VH lesion model as a predictive pharmacological screening assay for identifying compounds effective in the treatment of positive symptoms of schizophrenia. However, the usefulness of the model in detecting compounds effective in treating negative symptoms of schizophrenia is still in question.
Subject(s)
Animals, Newborn/physiology , Antipsychotic Agents/pharmacology , Clozapine/pharmacology , Hippocampus/injuries , Hippocampus/physiology , Risperidone/pharmacology , Schizophrenic Psychology , Acoustic Stimulation , Animals , Behavior, Animal/drug effects , Dose-Response Relationship, Drug , Female , Male , Motor Activity/drug effects , Pregnancy , Rats , Rats, Sprague-Dawley , Receptors, Dopamine D2/drug effects , Receptors, Dopamine D2/metabolism , Reflex, Startle/drug effects , Social BehaviorABSTRACT
RATIONALE: Many addictive drugs are known to have effects on learning and memory, and these effects could motivate future drug use. Specifically, addictive drugs may affect memory of emotional events and experiences in ways that are attractive to some users. However, few studies have investigated the effects of addictive drugs on emotional memory in humans. OBJECTIVES: This study examined the effects of the memory-enhancing drug dextroamphetamine (AMP) and the memory-impairing drug Δ(9)-tetrahydrocannabinol (THC) on emotional memory in healthy volunteers. METHODS: Participants completed three experimental sessions across which they received capsules containing placebo and two doses of either AMP (10 and 20 mg; N = 25) or THC (7.5 and 15 mg; N = 25) before viewing pictures of positive (pleasant), neutral, and negative (unpleasant) scenes. Memory for the pictures was assessed 2 days later, under drug-free conditions. RESULTS: Relative to placebo, memory for emotional pictures was improved by AMP and impaired by THC, but neither drug significantly affected memory for unemotional pictures. Positive memory biases were not observed with either drug, and there was no indication that the drugs' memory effects were directly related to their subjective or physiological effects alone. CONCLUSIONS: This study provides the first clear evidence that stimulant drugs can preferentially strengthen, and cannabinoids can preferentially impair, memory for emotional events in humans. Although addictive drugs do not appear to positively bias memory, the possibility remains that these drugs' effects on emotional memory could influence drug use among certain individuals.
Subject(s)
Dextroamphetamine/pharmacology , Dronabinol/pharmacology , Memory/drug effects , Adolescent , Adult , Cross-Over Studies , Dextroamphetamine/administration & dosage , Dose-Response Relationship, Drug , Double-Blind Method , Dronabinol/administration & dosage , Emotions , Female , Humans , Male , Young AdultABSTRACT
There is growing evidence that drugs of abuse alter processing of emotional information in ways that could be attractive to users. Our recent report that Δ9-tetrahydrocannabinol (THC) diminishes amygdalar activation in response to threat-related faces suggests that THC may modify evaluation of emotionally-salient, particularly negative or threatening, stimuli. In this study, we examined the effects of acute THC on evaluation of emotional images. Healthy volunteers received two doses of THC (7.5 and 15 mg; p.o.) and placebo across separate sessions before performing tasks assessing facial emotion recognition and emotional responses to pictures of emotional scenes. THC significantly impaired recognition of facial fear and anger, but it only marginally impaired recognition of sadness and happiness. The drug did not consistently affect ratings of emotional scenes. THC's effects on emotional evaluation were not clearly related to its mood-altering effects. These results support our previous work, and show that THC reduces perception of facial threat. Nevertheless, THC does not appear to positively bias evaluation of emotional stimuli in general.