Changing the general factor of personality and the c-fos gene expression with methylphenidate and self-regulation therapy

A deepening in the biological nature of the general factor of personality (GFP) is suggested: the activation level of the stress system is here represented by the gene expression of c-fos. The results of a single case experimental design are reported. A model of four coupled differential equations that explains the human personality dynamics as a consequence of a single stimulant drug intake has been fitted to psychological and biological experimental data. The stimulant-drug conditioning and its adaptation to the considered mathematical model is also studied for both kinds of measures. The dynamics of the c-fos expression presents a similar pattern to the dynamics of the psychological measures of personality assessed by the GFP-FAS (Five-Adjective Scale of the General Factor of Personality) as a consequence of a single dose of stimulant drug (methylphenidate). The model predicts similar dynamic patterns for both psychological and biological measures. This study proves that describing mathematically the dynamics of the effects of a stimulant drug as well as the effects of a conditioning method on psychological or subjective variables and on gene expression is possible. It verifies the existence of biological mechanisms underlying the dynamics of the General Factor of Personality (GFP).     

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.     

Forty years of methylphenidate treatment in Attention-Deficit/ Hyperactivity Disorder

This paper reviews approximately 40 years of stimulant drug treatment of children with behavior and learning problems. These patients generally fall under the rubric of Attention-Deficit/Hyperactivity Disorder (ADHD), with core symptoms of hyperactivity, impulsivity, and inattention being the most studied and most robust of the targets for stimulant treatment. In addition, the drug effects on other targets, such as cognitive and academic function, are included. The largest selection of studies involves methylphenidate. Both qualitative studies and meta-analytic studies from major reviews are examined. Variations in the methodology of the reviews are described and some of the discrepancies in interpretation examined. Despite wide variations in subject selection, types of trials, degree of methodological rigor, and the decade in which the studies took place, the evidence is remarkably consistent The overall results suggest significant clinical impact upon the core features of ADHD. More studies of long-term effects and special populations such as older adolescents and adults will be necessary, though existing evidence strongly supports similar findings as for the younger patients with a diagnosis of ADHD.     

Sensory phenomena in experimental nerve block

In the course of a series of blocks of the ulnar and lateral popliteal nerves of volunteers a study was made of the manner in which the responses of the subject to sensory stimulation become progressively altered and finally obliterated. These changes are described, together with the manner of recovery, and an account is given of various sensations induced by the blocking and the recovery processes. The relevant literature is briefly reviewed and possible factors involved in these phenomena are discussed.     

Anger arousal,deindividuation, and aggression

We tested the notion that angered persons' aggression would be increased through a process of excitation transfer when they are deindividuated, but that individuated subjects would be most aggressive in circumstances under which they could use the information that they had ingested an arousing drug as a pretext for their aggression. Sixty-two male undergraduates participated under either deindividuated or individuated conditions, ingested either 350 mg of caffeine or a placebo, were informed that they had either taken a stimulant or a nonarousing drug, and were all angered by a confederate. According to prediction, when deindividuated and aroused by caffeine the amount of noxious stimulation subjects delivered to the provocateur was greater if they believed that the drug they had taken was nonarousing than if they thought it was a stimulant; in contrast, individuated subjects' aggression was greater when aroused subjects believed the drug was a stimulant. The results are discussed in terms of excitation transfer and the effect of aggression inhibition on the use of information about one's arousal.     

Successful Child Psychotherapy of Attention Deficit/Hyperactive Disorder: An Agitated Depression Explanation

Science tries to explain phenomena in ways that are demonstrable and replicable to develop logical, coherent, parsimonious, and predictive theoretical systems. Yet hyperactive children are given stimulants to "calm" them down, despite the fact that science would predict stimulants would increase hyperactivity. Bradley (1937, 1950) observed that half of the behavior-problem children to whom he administered a stimulant for one week became subdued. He called this finding paradoxical, speculating that inhibitory centers of the central nervous system were stimulated. While Bradley's assertion of a paradoxical reverse effect in children may be an empirical observation, it is not an explanation. The Attention Deficit/Hyperactive Disorder (ADHD) is inferred to exist from hyperactive behavior, which in turn, is inferred to be neurological in origin, a circular argument. An inevitable consequence of the belief in the hypothetical neurological etiology of ADHD is that children are typically given stimulants. Using the case of a seven-year old child, described as experiencing ADHD, who was treated successfully without medication as an illustration, the author provides an alternative, more parsimonious explanation of the etiology, suggesting that ADHD is related to agitated depression.     

The role of drug use in a conceptual model of intimate partner violence in men and women arrested for domestic violence.

In a previous study, alcohol problems in perpetrators and their partners contributed directly and indirectly to intimate partner violence (IPV), even after including other correlates of violence in the model (G. L. Stuart et al., 2006). The present study extends these findings by examining the role of illicit drug use. We recruited 271 men and 135 women arrested for IPV and used structural equation modeling to examine the data. Results showed that drug use, as reported by the perpetrators, was a stronger predictor of IPV than were alcohol problems in perpetrators and their partners. Arrested males' marijuana use and stimulant use (i.e., cocaine and amphetamines) were associated with perpetration of IPV, and their report of their female partners' stimulant use was associated with her violence perpetration. In arrested women, specific substances used did not predict violence perpetration beyond other model variables; however, female perpetrators' report of male partners' stimulant use predicted male psychological and physical aggression, after controlling for other variables. These results provide further evidence that drug problems by both partners may be important in the evolution of aggression. Implications for batterer intervention programs are discussed.     

EEG Biofeedback for Addictive Disorders—The State of the Art in 2004

This paper reviews studies of brainwave biofeedback as a therapeutic technique for substance use disorder. This modality is attractive as a medication free, neurophysiologic, and self actualizing treatment for a substance based, brain impaired and self-defeating disorder. Three approaches are described and the literature for each reviewed. Alpha–theta occipital feedback was originally employed to facilitate autosuggestion in hypnagogic states to augment standard therapy approaches in substance abuse treatment programs and appears most suited for chronic treatment resistant alcoholics. Beta augmentation feedback in conjunction with alpha/theta feedback has been employed in mixed substance abuse and stimulant abuse with good results. Individualized brainwave biofeedback based on correcting EEG abnormalities, or based on addressing comorbid conditions is a third approach that has been described, and may be most appropriate where confounding comorbid conditions are present. Although effectiveness in certain hard to treat populations (conventional treatment resistant alcoholics, crack cocaine addicts, cognitively impaired substance abusers) is promising, better-designed controlled studies are needed.     

Callous-Unemotional Traits Modulate Brain Drug Craving Response in High-Risk Young Offenders

Adults with psychopathy have a high propensity for substance abuse, generally starting from a young age. This investigation tested hypotheses about differences in the neural responses associated with drug craving among high-risk young offenders with histories of abuse of stimulants and other drugs as a function of psychopathic traits. Fifty-four male adolescents (44 with a history of stimulant abuse and 10 controls) incarcerated at a maximum-security facility (M age = 17.08 years) completed a drug-cue exposure task while brain hemodynamic activity was monitored using functional magnetic resonance imaging (fMRI) with a mobile MRI scanner stationed at the facility. Psychopathic traits were assessed using the Hare Psychopathy Checklist: Youth Version (PCL:YV). In the stimulant abuser group, drug cues elicited activity in classic reward circuitry. Consistent with studies of adult psychopathic traits and substance abuse, there was a negative association between PCL-YV scores and hemodynamic response related to drug craving in the amygdala and ACC in youth with a history of stimulant abuse. However, there were considerably more negative associations between the PCL:YV and hemodynamic response among youth than adults and this was primarily due to callous-unemotional traits rather than interpersonal or behavioral traits. The implications for how personality traits modulate motivations for drug-seeking behavior among adolescent offenders are discussed.     

The use of psychopharmacology to study reciprocal influences in parent-child interaction

The present paper reviews the possible utility and limitations of using behavior-modifying drugs to study reciprocal influences in parent-child interactions. Ideal circumstances for use of this approach are outlined and contrasted with the current status of the field of psychopharmacology. Numerous limitations to the approach are found. Yet the utility of the design is demonstrated in several studies of stimulant drug effects on the mother-child interactions of hyperactive children, and in one pilot study of the effects of diazepam, an anxiolytic, on these same interactions. The major pitfalls to this approach will quite likely be overcome by future research and the development of safer, more highly specific behavior-modifying drugs.Funding for this paper is derived from Grant No. 1-R01-MH32334-01 from the National Institute of Mental Health.     

Incidence of infantile cerebral lesions in children with behavioral disorders]

The delimitation of behavioural disturbances predominantly due to organic brain lesions from those caused by reactions due to environmental factors has practical importance for drug therapy and pedagogic guidance. Figures on the incidence of infantile brain lesions among children with behavioural disorders range from between 20 to 90%. However, comparison of the results is difficult, because different authors followed different aspects for the evaluation of their material. The authors have collected data from 497 children from the 3 to 15 year-old age group who suffer from behavioural disturbances: history, neurological and psychological findings, electroencephalogram, native x-ray picture of the skull, pneumo-encephalogram and echoencephalogram were reviewed for signs and findings suggesting infantile brain damage. Certain signs of intantile brain lesion were found in 28.6% of the children. Among the apparative diagnostic procedures without impairment to the patients, the electroencephalogram proved particularly suited for the support of the diagnosis. The most accurate data on the localization and extent of the lesion are provided by the pneumo-encephalogram. However, its performance is not possible or justified in each child.     

HIV infection and drug users: Setting up support groups

The emergence of Human Immunodeficiency Virus (HIV) infection has highlighted the need for the development of risk reduction strategies among drug users. A network of support and self help, whilst fully developed among gay men, has been slow to develop with drug users. Possible reasons for this are examined. Examples of this type of approach in Britain and other countries are reviewed. The positive aspects of encouraging the development of self help groups are discussed. The lesons learned from the first 6 months of a drug users support group are described.     

The Efficacy, Safety, and Practicality of Treatments for Adolescents with Attention-Deficit/Hyperactivity Disorder (ADHD)

Studies examining interventions for adolescents diagnosed with attention-deficit/hyperactivity disorder (ADHD) were reviewed to evaluate their efficacy. These efficacy findings were supplemented with a preliminary system for judging safety and practicality. Results suggest that the stimulant drug methylphenidate (MPH) is safe and well-established empirically, but has some problems with inconvenience and noncompliance. Preliminary research supports the efficacy, safety, and practicality of some psychotherapeutic interventions, including behavioral classroom interventions, note-taking training, and family therapy. Treatment with tricyclic antidepressants was judged to have minimal empirical support and debatable safety. Very little is known about long-term effectiveness of treatments, long-term compliance, or multimodal treatments for adolescents such as stimulants plus behavior therapy.     

Sensation seeking, augmenting-reducing, and the perceived and preferred effects of drugs

The following measures were administered to 78 undergraduates: the General and Disinhibition subscales of Zuckerman's (1971) Sensation-Seeking Scale; the Reducer-Augmenter Scale (RAS; Vando, 1970, 1974); self-reported use of alcohol, tobacco, and cannabis; the degree of attribution of stimulant, depressant, and neutral effects to these drugs; and desirability ratings of stimulant and depressant effects ascribed to various drugs. Major findings were as follows: (a) On the RAS, reducing correlated positively with both sensation-seeking measures. (b) Seven of the nine personality-versus-drug-use correlations were positive and significant. (c) Generally, the effects attributed to drugs did not differ by sex, personality, or use. (d) However, frequent drinkers attributed stimulant effects to alcohol more strongly than depressant effects, whereas infrequent drinkers did the opposite. (e) The mean desirability ratings of stimulant and depressant drug effects correlated positively. (f) High disinhibitors rated drug effects of both kinds more favorably than did lows. (g) A similar, more favorable evaluation by high than by low general sensation seekers was significant for male subjects only. (h) Score on the Reducer-Augmenter Scale was not significantly predictive of subjects' desirability ratings.     

Neuropsychological evaluation in the assessment of personal injury

Neuropsychological evaluation offers unique potentials in the assessment of personal injury claims. Strengths and limitations of major approaches to testing are reviewed, and special attention is given to applications in the particular forensic areas of head injury, toxic environments, physical disease, and malpractice. The varieties of cognitive, emotional, and interpersonal damages which may occur with brain injury are described. Suggestions are provided for forensically appropriate neuropsychological assessment, as well as guidelines offered for discerning inappropriate practices. Issues of neurological malingering, credentialing of the expert, and forensic roles of the neuropsychologist in rehabilitation are discussed.     

Drug dreams: a neuropsychoanalytic hypothesis

Recent studies have shown that the ventral tegmental pathway stimulates both dreaming and drug craving. To investigate a possible clinical link between these two psychic phenomena, psychotherapy notes from the first six months of an addicted patient's treatment were reviewed, together with verbatim notes from the four years of psychoanalysis that followed. Of 240 dreams reported by the patient,58 had manifest content involving the seeking or using of drugs. There was no particular temporal or emotional thematic pattern to these "drug dreams,"which persisted through four and a half years of sobriety. Drug dreams are observable phenomena that reflect both the innate structure of the brain and neural changes produced by exposure to addictive drugs. In some addicted persons, exposure to drugs produces a fixed change in neurological functioning with which they must contend for years, possibly the rest of their lives. Drug craving meets Freud's defining characteristics for a drive: it is a constant pressure, originating from within the organism, to do work, and it constantly demands satisfaction. Because ego and libidinal drives share a common neural pathway, they should not be separated conceptually. Solms's finding (in press) that the activating systems for dreaming and for craving are identical, a finding based on observations of tumor- or stroke-provoked brain lesions, is confirmed by observation of the dreams of a patient whose brain changes were created by drug exposure. This study provides further evidence that the origin of the dream is a wish.     

Stimulant-induced adaptations in neostriatal matrix and striosome systems: transiting from instrumental responding to habitual behavior in drug addiction

Converging evidence indicates that repeated exposure to motor stimulants such as cocaine and amphetamine produces marked alterations in network responsiveness of striatal neurons to subsequent challenge with the same stimulant drug. Such alterations, which correlate with persistent patterns of repetitive behavior, associate with distinct compartmental changes in the neostriatum. Striatal matrix system neurons undergo "silencing" following repeated drug challenges, allowing striosome system neurons to exhibit preferential activation. Matrix neurons are innervated by sensory and motor areas of neocortex and are activated in the course of on-going, adaptive behavior. Inactivation of matrix neurons by chronic stimulant exposure may therefore constrain sensorimotor and cognitive processing. In turn, the striosomes are anatomically connected through re-entrant loops with limbic prefrontal and allocortical structures, such as anterior cingulate cortex, orbital frontal cortex, and basolateral amygdala, all of which play a part in stimulant-induced reinforcement and relapse to drug-taking. Moreover, functional evidence links striosome system neurons, which are responsible for providing inhibitory regulatory feedback to midbrain dopamine neurons, with reinforcement-based processes. In considering such evidence, we postulate that recurrent matrix inactivation and recruitment of striosome-based pathways by chronic stimulant exposure represent neural end-points of the transit from action-outcome associative behavior to conditioned habitual responding. Within this theoretical framework, habitual behavior can be elicited by both interoceptive cues and exteroceptive conditioned stimuli to promote the automatic execution of learned responses.     

A four-year follow-up study of the effects of methylphenidate on the behavior and academic achievement of hyperactive children

Sixty-two children were evaluated 4 years after their initial referral for symptoms of hyperactivity. Behavioral measures included parent and teacher judgments of behavior and social adjustment. Academic achievement was assessed by teachers' reports, number of failed grades, special education services, and two individually administered achievement tests. Data were analyzed for the total group to determine both the extent to which presenting problems diminished over time and the major problems still present. The effects of stimulant drug therapy on outcome were assessed by dividing the children into groups according to the duration of time they had taken stimulants. Total duration of time on stimulants ranged from less than 6 months (group 1) to 4 years (group 5). Results indicated that the symptoms of hyperactivity significantly lessened, but remained higher in these children than in normal peers. Behavioral and social problems were less pervasive than academic underachievement. There were no group differences, indicating that the duration of stimulant intervention did not have a significant effect on outcome. The clinical implication of this study is that the beneficial effects of stimulant drug intervention occur within the first months after initiation of therapy. Long-term treatment does not appear to be of value in producing better outcome.     

Methylphenidate and cognitive therapy: A comparison of treatment approaches with hyperactive boys

This study of hyperactive boys evaluated the effects of three modes of treatment in relation to an untreated group. The treatments were administered over a 3-month period and included cognitive training, stimulant drug therapy (methylphenidate), and the two treatments combined. A follow-up assessment was conducted approximately 3 months after contact between the training staff and the child had ceased. Analyses of attentional deployment and cognitive style measures, tests of academic achievement, and behavioral ratings showed that only those children in the two medication treatment conditions demonstrated improvement in attentional deployment and behavioral ratings. In the cognitive therapy condition, there were changes only on measures of attentional deployment. The data did not provide evidence indicating that the combined medication and cognitive therapy condition was any more effective than that condition involving medication alone. Discussion provides future guidelines for evaluation of the relative effectiveness of stimulant drug therapy and other psychological treatment modalities.