Bayesian Diagnostics of Hidden Markov Structural Equation Models with Missing Data

Cocaine is a type of drug that functions to increase the availability of the neurotransmitter dopamine in the brain. However, cocaine dependence or abuse is highly related to an increased risk of psychiatric disorders and deficits in cognitive performance, attention, and decision-making abilities. Given the chronic and persistent features of drug addiction, the progression of abstaining from cocaine often evolves across several states, such as addiction to, moderate dependence on, and swearing off cocaine. Hidden Markov models (HMMs) are well suited to the characterization of longitudinal data in terms of a set of unobservable states, and have increasingly been used to uncover the dynamic heterogeneity in progressive diseases or activities. However, the existence of outliers or influential points may misidentify the hidden states and distort the associated inference. In this study, we develop a Bayesian local influence procedure for HMMs with latent variables in the presence of missing data. The proposed model enables us to investigate the dynamic heterogeneity of multivariate longitudinal data, reveal how the interrelationships among latent variables change from one state to another, and simultaneously conduct statistical diagnosis for the given data, model assumptions, and prior inputs. We apply the proposed procedure to analyze a dataset collected by the UCLA center for advancing longitudinal drug abuse research. Several outliers or influential points that seriously influence estimation results are identified and removed. The proposed procedure also discovers the effects of treatment and individuals’ psychological problems on cocaine use behavior and delineates their dynamic changes across the cocaine-addiction states.     

Extinction training regulates neuroadaptive responses to withdrawal from chronic cocaine self-administration

Cocaine produces multiple neuroadaptations with chronic repeated use. Many of these neuroadaptations can be reversed or normalized by extinction training during withdrawal from chronic cocaine self-administration in rats. This article reviews our past and present studies on extinction-induced modulation of the neuroadaptive response to chronic cocaine in the mesolimbic dopamine system, and the role of this modulation in addictive behavior in rats. Extinction training normalizes tyrosine hydroxylase levels in the nucleus accumbens (NAc) shell, an effect that could help ameliorate dysphoria and depression associated with withdrawal from chronic cocaine use. Extinction training also increases levels of GluR1 and GluR2/3 AMPA receptor subunits, while normalizing deficits in NR1 NMDA receptor subunits, in a manner consistent with long-term potentiation of excitatory synapses in the NAc shell. Our results suggest that extinction-induced increases in AMPA and NMDA receptors may restore deficits in cortico-accumbal neurotransmission in the NAc shell and facilitate inhibitory control over cocaine-seeking behavior. Other changes identified by gene expression profiling, including up-regulation in the AMPA receptor aggregating protein Narp, suggest that extinction training induces extensive synaptic reorganization. These studies highlight potential benefits for extinction training procedures in the treatment of drug addiction.     

Interaction of the Dopaminergic System With Mechanisms of Associative Learning and Cognition:Implications for Drug Abuse

The possible role of mechanisms of associative learning in drug abuse and addiction is considered with respect to psychomotor stimulant drugs such as cocaine and amphetamine. Although the initial sites of the reinforcing effects of these drugs are associated with the mesolimbic dopamine projection to the nucleus accumbens, other important neuromodulatory influences are identified. These include the amygdala, which appears to mediate the associative processes by which environmental stimuli come to control drug-seeking behavior. Possible parallel mechanisms by which stimulant drugs enhance effects of aversive as well as rewarding stimuli are discussed. The importance of attribution and context in determining relative rewarding and aversive effects is pointed out. These attributional and contextual factors may be a function of cortical regions that may themselves be impaired by chronic drug abuse, leading to further dysexecutive control over cognition and behavior.     

Substance abuse and violence: A review of the literature

Most alcohol and drug use occurs among persons who are not violent. However, alcohol and, to a lesser extent, illicit drugs are present in both offenders and victims in many violent events. The links between psychoactive substances and violence involve broad social and economic forces, the settings in which people obtain and consume the substance, and the biological processes that underlie all human behavior. In the case of alcohol, evidence from laboratory and empirical studies support the possibility of a causal role in violent behavior. Similarly, the psychopharmacodynamics of stimulants, such as amphetamines and cocaine, also suggest that these substances could play a contributing role in violent behavior. On the other hand, most real-world studies indicate that this relationship is exceedingly complex and moderated by a host of factors in the individual and the environment. In addition to psychopharmacological effects, substance use may lead to violence through social processes such as drug distribution systems (systemic violence) and violence used to obtain drugs or money for drugs (economic compulsive violence).     

Evaluating the relative effectiveness of three aversion therapies designed to reduce craving among cocaine abusers

Crack cocaine use and dependence has been steadily increasing since the mid‐1980s. Treatment approaches vary from simple psychotherapy to intensive medication regimens. One clear phenomenon that has been implicated in the continued use and abuse of crack cocaine is craving. Craving is believed to be a response that has been conditioned with previous drug using episodes, and is elicited by environmental cues. The current study investigated the use of three aversion therapies (chemical, covert sensitization, and faradic) designed to eliminate craving for cocaine. Seventy subjects were randomly assigned to one of three aversion treatments or a relaxation control condition. Results indicate that aversion therapy reduces crack cocaine craving. The use of aversion therapy as an adjunct to traditional treatment programs for reducing craving is discussed. Copyright © 2004 John Wiley & Sons, Ltd.     

Error monitoring recovery after abstinence and treatment in cocaine addicts / Recuperación del procesamiento de errores tras abstinencia y tratamiento en adictos a cocaína

Abstract

Cocaine addiction is associated with different cognitive functions. Error monitoring and inhibition of behaviour are of great significance, they are specifically relevant because of their connection with problems in decision making and relapse. The aim of this work is to not only study the deficits but also to see if recovery is possible after treatment and abstinence. We evaluated 23 participants with cocaine dependence and 23 control subject with a modification of the Eriksen Flanker Task. Participants with addiction showed lower scores than control subjects in congruent and incongruent conditions. As treatment time increased the number of correct responses improved, especially in post-error hits. We conclude that the processes of rehabilitation and detoxification could improve the ability to monitor errors and inhibiting behaviour.     

Withdrawal from cocaine self-administration produces long-lasting deficits in orbitofrontal-dependent reversal learning in rats

Drug addicts make poor decisions. These decision-making deficits have been modeled in addicts and laboratory animals using reversal-learning tasks. However, persistent reversal-learning impairments have been shown in rats and monkeys only after noncontingent cocaine injections. Current thinking holds that to represent the human condition effectively, animal models of addiction must utilize self-administration procedures in which drug is earned contingently; thus, it remains unclear whether reversal-learning deficits caused by noncontingent cocaine exposure are relevant to addiction. To test whether reversal learning deficits are caused by contingent cocaine exposure, we trained rats to self-administer cocaine, assessed cue-induced cocaine seeking in extinction tests after 1 and 30 d of withdrawal, and then tested for reversal learning more than a month later. We found robust time-dependent increases in cue-induced cocaine seeking in the two extinction tests (incubation of craving) and severe reversal-learning impairments.     

Risk Factors for Attempting Suicide in Heroin Addicts

In order to examine risk factors for attempting suicide in heroin dependent patients, a group of 527 abstinent opiate dependent patients had a psychiatric interview and completed the Childhood Trauma Questionnaire. Patients who had or had never attempted suicide were compared on putative suicide risk factors. It was found that 207 of the 527 heroin abusers (39.3%) had attempted suicide. Attempters were younger; more were female, reported childhood trauma, a family history of suicidal behavior, a history of aggression, treatment with antidepressant medication, and alcohol and cocaine dependence. Logistic regression revealed that a family history of suicidal behavior, alcohol dependence, cocaine dependence, and treatment with antidepressant medication were significant predictors of attempting suicide. These results suggest that attempting suicide is common among opiate dependent patients and that both distal and proximal risk factors may play a role.     

Effects of cocaine and d-amphetamine on the repeated acquisition and performance of conditional discriminations.

The acute and chronic effects of cocaine and d-amphetamine on food-reinforced behavior were investigated in pigeons responding on a two-component multiple schedule. In one component, the behavioral task consisted of the same chain of conditional discriminations each session (performance). In the other component, the chain of conditional discriminations was changed from session to session (learning). In comparison to control sessions, both acute cocaine and d-amphetamine increased errors in each component of the multiple schedule. Responding in the learning component, however, was generally disrupted at lower doses than those that affected responding in the performance component. At high doses, both drugs produced pauses in responding in each component in three of the four subjects. Pausing engendered by d-amphetamine was approximately twice as long as that under cocaine. Upon chronic administration, both the pausing and error-increasing effects of each drug diminished. Drug-induced changes in timeout responding, however, did not decrease during chronic administration. Redeterminations of the d-amphetamine dose-effect curves following chronic cocaine administration suggested the existence of cross-tolerance between cocaine and d-amphetamine. Both the acute and chronic data are consistent with the view that conditions of stimulus control may modulate the behavioral effects of drugs.     

Analysis of fixed-ratio behavior maintained by drug reinforcers.

Behavior maintained by intravenously delivered alfentanil, cocaine, or ketamine was assessed using a fixed-ratio schedule of reinforcement. As the dose of each drug was increased, rate of responding also increased up to a maximum. Further increases in dose resulted in decreased response rates (inverted U-shaped curve). An analysis of postreinforcement-pause-time and run-time measures for the ascending limb of the inverted U-shaped functions revealed that behavior was characterized by systematic decreases in both pause time and run time as dose and rate increased. An examination of the descending limb of the dose-response functions revealed that lowered response rates for cocaine and ketamine were correlated with increases in run time and small and inconsistent effects on postreinforcement pause time. Behavior maintained by rate-reducing doses of alfentanil was characterized by lengthened postreinforcement pauses with small increases in run time. These data suggest that at larger doses, drug reinforcers may have unconditioned or direct effects on the behavior that the drug is maintaining, and more important, that the nature of these unconditioned effects depends on the drug that is maintaining behavior.     

Substance use/abuse as a predictor to illegal and violent behavior: A review of the relevant literature

The preponderance of the research evidence supports the conclusion that abuse of certain types of illicit drugs, separately from the abuse of alcohol, predisposes to subsequent violent behavior. The relationship of cocaine/crack to violent crime has been established more clearly for users of crack in inner city areas than it has for those who are users of other forms of cocaine in the general population.In regard to any race/ethnic or socioeconomic factors in the relationships between substance use/abuse and violent behavior, most clearly established is that a higher proportion of young Black males, compared to other race/ethnic groups, are actively involved in dealing cocaine/crack in some inner city poverty areas.As for gender differences, the research evidence indicates that alcohol abuse as a predictor to and a precipitant of violent behavior, is more clearly established for males than for females. Drug abuse, as distinct from alcohol abuse, has been found to predict subsequent violent behavior, for females as well as for males. “Co-morbidity,” the combination of substance use with and psychopathology, appears more likely to predict for females to later violent behavior. Psychopathology and mental health problems are less likely to predict occurrence of either violent or criminal behavior in the future than are either alcohol abuse or drug abuse.     

Impaired goal-directed behavioural control in human impulsivity

Two dissociable learning processes underlie instrumental behaviour. Whereas goal-directed behaviour is controlled by knowledge of the consequences, habitual behaviour is elicited directly by antecedent Pavlovian stimuli without knowledge of the consequences. Predominance of habitual control is thought to underlie psychopathological conditions associated with corticostriatal abnormalities, such as impulsivity and drug dependence. To explore this claim, smokers were assessed for nicotine dependence, impulsivity, and capacity for goal-directed control over instrumental performance in an outcome devaluation procedure. Reduced goal-directed control was selectively associated with the Motor Impulsivity factor of Barrett's Impulsivity Scale (BIS), which reflects propensity for action without thought. These data support the claim that human impulsivity is marked by impaired use of causal knowledge to make adaptive decisions. The predominance of habit learning may play a role in psychopathological conditions that are associated with trait impulsivity.     

Substance use/abuse as a predictor to illegal and violent behavior: A review of the relevant literature

The preponderance of the research evidence supports the conclusion that abuse of certain types of illicit drugs, separately from the abuse of alcohol, predisposes to subsequent violent behavior. The relationship of cocaine/crack to violent crime has been established more clearly for users of crack in inner city areas than it has for those who are users of other forms of cocaine in the general population.In regard to any race/ethnic or socioeconomic factors in the relationships between substance use/abuse and violent behavior, most clearly established is that a higher proportion of young Black males, compared to other race/ethnic groups, are actively involved in dealing cocaine/crack in some inner city poverty areas.As for gender differences, the research evidence indicates that alcohol abuse as a predictor to and a precipitant of violent behavior, is more clearly established for males than for females. Drug abuse, as distinct from alcohol abuse, has been found to predict subsequent violent behavior, for females as well as for males. “Co-morbidity,” the combination of substance use with and psychopathology, appears more likely to predict for females to later violent behavior. Psychopathology and mental health problems are less likely to predict occurrence of either violent or criminal behavior in the future than are either alcohol abuse or drug abuse.     

Neuronal substrates of relapse to cocaine-seeking behavior: role of prefrontal cortex

The return to drug seeking, even after prolonged periods of abstinence, is a defining feature of cocaine addiction. The neural circuitry underlying relapse has been identified in neuropharmacological studies of experimental animals, typically rats, and supported in brain imaging studies of human addicts. Although the nucleus accumbens (NAcc), which has long been implicated in goal-directed behavior, plays a critical role in this circuit, the prefrontal cortex (PFC) appears to process the events that directly trigger relapse: exposure to acute stress, cues previously associated with the drug, and the drug itself. In this paper, we review animal models of relapse and what they have revealed about the mechanisms underlying the involvement of the NAcc and PFC in cocaine-seeking behavior. We also present electrophysiological data from PFC illustrating how the hedonic, motor, motivational, and reinforcing effects of cocaine can be analyzed at the neuronal level. Our preliminary findings suggest a role for PFC in processing information related to cocaine seeking but not the hedonic effects of the drug. Further use of this recording technology can help dissect the functions of PFC and other components of the neural circuitry underlying relapse.     

CONTINGENT REINFORCEMENT OF ABSTINENCE WITH INDIVIDUALS ABUSING COCAINE AND MARIJUANA

Two males diagnosed with cocaine dependence received a behavioral intervention comprised of contingency management and the community reinforcement approach. During the initial phase of treatment, reinforcement was delivered contingent on submitting cocaine-free urine specimens. The community reinforcement approach involved two behavior therapy sessions each week. Almost complete cocaine abstinence was achieved, but regular marijuana use continued. During a second phase, reinforcement magnitude was reduced, but remained contingent on submitting cocaine-free specimens. Behavior therapy was reduced to once per week. Cocaine abstinence and regular marijuana use continued. Next, reinforcement was delivered contingent on submitting cocaine- and marijuana-free specimens. This modified contingency resulted in an abrupt increase in marijuana abstinence and maintenance of cocaine abstinence. One- and 5-month follow-ups indicated that cocaine abstinence continued, but marijuana smoking resumed. These results indicate that the behavioral intervention was efficacious in achieving abstinence from cocaine and marijuana; maintenance, however, was achieved for cocaine only.     

Predictors of decision-making on the Iowa Gambling Task: independent effects of lifetime history of substance use disorders and performance on the Trail Making Test

Poor decision-making and executive function deficits are frequently observed in individuals with substance use disorders (SUDs), and executive deficits may contribute to poor decision-making in this population. This study examined the influence of lifetime history of an alcohol, cocaine, heroin, or polysubstance use disorder on decision-making as measured by the Iowa Gambling Task (IGT) after controlling for executive ability, demographic characteristics, and current substance use. Participants (131 with lifetime history of SUD and 37 controls) completed the IGT and two neuropsychological tests: the Trail Making Test and the Controlled Oral Word Association Test. Control participants performed significantly better than those with a lifetime SUD history on the IGT, but performance on the neuropsychological tests was comparable for the two groups. A lifetime SUD diagnosis was associated with performance on the IGT after controlling for covariates, and Trail Making Test performance was associated with IGT performance in both SUD and control participants.     

A neural plasticity perspective on the schizophrenic condition

Imbalanced plasticity of neural networks in the brain is proposed to underlie deficits in the integration of efferent and afferent processes in schizophrenia. These deficits affect the priming of the behavior implementing systems by prior knowledge, and thus impair both controlled regulation and automatic activation of mental and motor processes. The sense of self as a distinct entity can consequently be undermined. In predominantly reality-distorting patients, hypo-plasticity of neural connectivity may cause the emergence of highly focused but inflexible patterns of activation in their representation and response systems. This may lead to dominance of prepotent patterns of activity in these systems and a relative inability of higher control systems to bias lower level activity towards congruence with the ongoing cognitive and motor context. By contrast, predominantly disorganized patients are characterized by hyper-plastic connectivity. This leads to a weakening of prepotent response tendencies but also, as in reality-distorting patients, to less effective top-down contextual constraining.     

Individual Religiosity,Moral Community,and Drug User Treatment

Some scholars have suggested that individual religiosity inhibits deviant behavior. Others have suggested that behavior is more responsive to the influence of religiously‐oriented moral communities than to the religiosity of individuals. Still others have suggested that non‐religious moral communities, such as sports teams or self‐help recovery groups, are just as effective as religious moral communities. The current article examines the associations between addicts' reductions in drug and alcohol use and religiosity, increase in church attendance, and increase in addiction self‐help recovery group attendance, following participation in publicly funded treatment programs. Results indicate that increase in self‐help recovery group attendance and church attendance were independently associated with reduction in alcohol use. Only increase in church attendance was significantly associated with reduction in cocaine use. Self‐assessed religious conviction was not associated with changes in drug use.     

Cocaine tolerance: acute versus chronic effects as dependent upon fixed-ratio size.

The effects of cocaine on operant behavior were studied by examining fixed-ratio value as a factor in the development of tolerance. Pigeons pecked a response key under a three-component multiple schedule, with each bird being exposed to fixed-ratio values that were categorized as small, medium, or large. Administered acutely, cocaine (1.0 to 10.0 mg/kg) produced dose-related decreases in overall rate of responding. Responding maintained by the largest ratio was decreased by lower doses than those required to reduce rates of responding maintained by the other two ratio schedules. Following repeated daily administration of 5.6 mg/kg of cocaine, dose-effect functions (obtained from sessions during the chronic regimen by making substitutions for the daily dose) indicated tolerance under the smaller ratios, but no tolerance or less tolerance under the largest ratio. Thus, whether tolerance developed, and the degree to which it developed, depended on the ratio value. The results are partially consistent with the notion that tolerance to drug effects on schedule-controlled behavior will develop if drug administration initially reduces reinforcement frequency, but they indicate that reinforcement loss alone is not a sufficient condition for the generation of tolerance under such conditions. The findings suggest that amount of responding required for reinforcement, or "effort," may contribute to the development of tolerance to effects of cocaine.