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PubMed2001

Addiction and the brain: the neurobiology of compulsion and its persistence.

People take addictive drugs to elevate mood, but with repeated use these drugs produce serious unwanted effects, which can include tolerance to some drug effects, sensitization to others, and an adapted state - dependence - which sets the stage for withdrawal symptoms when drug use stops. The most serious consequence of repetitive drug taking, however, is addiction: a persistent state in which compulsive drug use escapes control, even when serious negative consequences ensue. Addiction is characterized by a long-lasting risk of relapse, which is often initiated by exposure to drug-related cues. Substantial progress has been made in understanding the molecular and cellular mechanisms of tolerance, dependence and withdrawal, but as yet we understand little of the neural substrates of compulsive drug use and its remarkable persistence. Here we review evidence for the possibility that compulsion and its persistence are based on a pathological usurpation of molecular mechanisms that are normally involved in memory.

Animals↗
PubMed2001

Adiposity indices in German children and adolescents with genetically confirmed Prader-Willi syndrome (PWS).

BACKGROUND: Morbid obesity develops as a result of hyperphagia and compulsive eating behavior in patients with Prader-Willi syndrome (PWS), if caloric intake is not rigorously controlled. PWS-specific centile curves for adiposity indices constructed in the past were based on clinically diagnosed patients. With the advent of molecular genetic methods, allowing for an unequivocal diagnosis, new PWS curves based exclusively on molecularly diagnosed patients are becoming available, eliminating a potential diagnostic bias. OBJECTIVE: To compare fat distribution in molecularly confirmed German PWS patients to that of clinically diagnosed American PWS patients and a healthy reference population. DESIGN: Cross-sectional anthropometric study. SUBJECTS: One hundred German patients (49 F) with molecularly confirmed PWS (age: <30 y). MEASUREMENTS: Triceps (subscapular) skinfold thickness, waist and hip circumference. RESULTS: Skinfold thickness was massively elevated in the majority of the molecularly confirmed German PWS patients compared to a healthy reference population. Whereas triceps skinfold thickness was in good agreement with American PWS patients, subscapular skinfold thickness in German girls rose earlier than in American PWS girls, indicating possible differences between caloric intake or the proportion of patients entering puberty spontaneously. Waist circumference and waist-hip ratio (n=89) were elevated in a relative small proportion of patients only and did not reflect lower abdominal fat. This may be due to the peculiar shape of many patients with a typical fat accumulation around the buttocks. CONCLUSIONS: In addition to body mass index, use of skinfold thickness is recommended for follow-up of dietary interventions in PWS.

Adolescent↗
PubMed2005

The anxiogenic drug yohimbine reinstates palatable food seeking in a rat relapse model: a role of CRF1 receptors.

The major problem in treating excessive eating is high rates of relapse to maladaptive eating habits during diet treatments; this relapse is often induced by stress or anxiety states. Preclinical studies have not explored this clinical problem. Here, we adapted a reinstatement model (commonly used to study relapse to abused drugs) to examine the role of stress and anxiety in relapse to palatable food seeking during dieting. Rats were placed on restricted diet (75-80% of daily standard food) and for 12 intermittent training days (9 h/day, every other day) lever-pressed for palatable food pellets (25% fat, 48% carbohydrate) under a fixed ratio 1 (20-s timeout) reinforcement schedule. Subsequently, the rats were given 10 daily extinction sessions during which lever presses were not reinforced, and were then injected with yohimbine (an alpha-2 adrenoceptor antagonist that induces stress and anxiety in humans and non-humans) or given a single food pellet to assess reinstatement of food seeking. The rats rapidly learned to lever press for the palatable pellets and across the training days the ratio of timeout nonreinforced lever presses to reinforced lever presses progressively increased more than three-fold, suggesting the development of compulsive eating behavior. After extinction, yohimbine injections and pellet priming reliably reinstated food seeking. The corticotropin-releasing factor1 (CRF1) receptor antagonist antalarmin attenuated the reinstatement induced by yohimbine, but not pellet priming. Antalarmin also reversed yohimbine's anxiogenic effects in the social interaction test. These data suggest that CRF is involved in stress-induced relapse to palatable food seeking, and that CRF1 antagonists should be considered for the treatment of maladaptive eating habits.

Adrenergic alpha-Antagonists↗
PubMed1998

The latent variable structure of the Compulsive Behaviour Checklist in people with Prader-Willi syndrome.

The presence and severity of compulsive behaviours may be evaluated via the Compulsive Behaviour Checklist (CBC) and this instrument has been successfully employed in people with intellectual disability. However, the applicability of the overall CBC scoring system, which entails tallying the number of behavioural categories represented (i.e. five) as well as the number of individual behaviours endorsed (i.e. 25), is not known in the population with Prader-Willi syndrome (PWS). The present investigation examined the latent variable structure of the CBC in people with PWS in order to identify possible population-specific scoring and interpretation considerations. The 25 behaviour-specific items of the CBC were analysed for 75 people with PWS (44 females and 31 males) aged between 4 and 41 years (mean +/- SD = 11.4+/-9.4) via factor analysis with principal component extraction and equamax rotation. The most suitable solution was determined on the basis of multiple empirical criteria: (1) the scree test; (2) eigenvalues >1.00; (3) salient loadings >0.30; (4) the clarity of item assignment to a single latent dimension; (5) the internal consistency of the latent dimension(s) (coefficient alpha > or = 0.70); and (6) item-total correlations between 0.20 and 0.79. In addition, solutions were examined with respect to psychological theory and previous research. A 'general factor' (i.e. single latent dimension) solution which adhered to all a priori criteria was indicated. Twenty-four out of 25 items achieved salient loadings ranging from 0.46 to 0.80 on the general factor. The single item which failed to achieve salience, 'deviant grooming-skin picking', exhibited both substantial unique variance (0.997) and moderate reliability (r = 0.59, P<0.001). The internal consistency of the general factor was strong (alpha = 0.93) and all salient items were suitably correlated with the unit-weighted total score (r(item-total) = 0.41-0.77). The traditional CBC scoring system, which includes tallying the number of categories represented, would not be relevant in this PWS sample. In addition, the recommended tallying of the number of individual behaviours endorsed does not reflect the empirically indicated notion of compulsive behaviour in this special population. These findings indicate that the 24 salient items should be scored as a unit-weighted composite and that the score on the substantially unique item (skin picking) should be considered a separate measure when evaluating compulsive behaviours via the CBC in people with PWS.

Adolescent↗
PubMed1970

Evidence for transfer of enzyme product as the basis of metabolic cooperation between tissue culture fibroblasts of Lesch-Nyhan disease and normal cells.

Tissue culture fibroblasts derived from patients with Lesch-Nyhan disease (congenital hyperuricosuria) have a reduced IMP:pyrophosphate phosphoribosyltransferase (EC 2.4.2.8) activity and therefore incorporate, as detected by radioautography, much smaller amounts of tritiated hypoxanthine or guanine into cell nuclei and cytoplasm than do normal cells. However, Lesch-Nyhan cells grown in close contact with normal fibroblasts incorporate these purines. This phenomenon, which requires cell to cell contact for correction of the mutant phenotype, has been called metabolic cooperation. After separation of Lesch-Nyhan cells from normal cells, there is a prompt reversion to the mutant phenotype although the transferase is stable under these conditions for many hours.These results are most compatible with the transfer from normal to mutant fibroblasts of the product of the normal enzyme, a nucleotide or a nucleotide derivative, rather than the transfer of the transferase or informational macromolecules leading to the synthesis of the enzyme. Metabolic cooperation may provide a mechanism for maintaining normal cell function in the heterozygote in vivo. Evidence has been presented previously that selection of normal cells, presumably during embryogenesis, also provides a means for achieving normal function in the heterozygote.

Clinical Enzyme Tests↗
PubMed2003

Disrupted facial empathy in drawings from artists with frontotemporal dementia.

The sense of empathy may be altered by brain disease. We report the drawing performance of four artists who developed frontotemporal dementia (FTD). The first three, but not the fourth, had a prominent decrease in empathy for others as well as alterations in their caricatures of people. Their drawings of faces became distorted, menacing, skeleton-like, or 'alien'. None of the four had facial recognition difficulties, problems in interpreting facial emotions, or a decreased appreciation of the distinction between animate and inanimate objects. Functional brain imaging in the patients revealed bilateral frontal hypometabolism or hypoperfusion, and the three with altered drawings had additional prominent involvement of the right temporal lobe. These FTD patients and the literature suggest that FTD, possibly with greater right temporal involvement, disrupts the sense of empathy from human faces.

Activities of Daily Living↗
PubMed2006

Life events and benign paroxysmal positional vertigo: a case-controlled study.

CONCLUSIONS: Within the poorly understood mechanisms implicated in the aetiology of benign paroxysmal positional vertigo (BPPV), the results of this trial provide clinical evidence of a potential role of emotional stress connected to adverse life events as a trigger of otoconial dysfunction. High levels of anxiety, depression and somatization were recorded and considered psychogenic precursors of BPPV, thus emphasizing the role of psychological distress in precipitating peripheral vestibular disorders. Therefore, appraisal of life stress and psychological attitudes may have potential implications in the clinical assessment of this labyrinthine vertigo and its frequent relapses. OBJECTIVES: BPPV is one of the most common peripheral vestibular disorders, and although it has been the subject of several studies and debates, its aetiology still remains unknown in most cases. Because it has been shown that emotional stress is related to the onset or worsening of other inner ear dysfunctions such as Ménière's disease and sudden hearing loss, this study investigated the hypothesis that life events, mood and psychological attitudes may have a causal relationship with BPPV. PATIENTS AND METHODS: Fifty patients (40 females and 10 men; mean age 43.5+/-10.1 years, range 30-65 years) were recruited and compared with 50 healthy volunteers matched for sex, age and socio-demographic variables. Patients were selected among dizzy patients who were referred to the ENT Clinic of the University of Modena and Reggio Emilia from the emergency unit with a primary diagnosis of 'positional vertigo' and enrolled in the study only if they had a paroxysmal positional nystagmus as diagnosed by Dix-Hallpike and Semont's manoeuvres. Patients with a history of recurrent vertigo and additional otoneurological diseases were excluded. The Paykel Life Events Scale, Spielberger State-Trait Anxiety Inventory, Symptom Check List-90 Revisited and Hamilton Depression Scale were the psychometric questionnaires used to complete the audiological and vestibular examinations. RESULTS: Patients with BPPV reported significantly more life events than control subjects in the year preceding the onset of vertigo (p<0.005). Negative life events, objective negative impact and a poor degree of control were also significantly more frequent in patients compared with controls (p<0.005). There were no significant differences between groups concerning positive life events (p>0.05). Psychometric questionnaires recorded significantly higher levels of anxiety, depression and somatization in the pathological sample (p<0.005), as well as an increased obsessive-compulsive attitude (p<0.05).

Adult↗
PubMed1987

Type A coronary-prone behaviour pattern and pathological narcissism.

Type A coronary-prone behaviour pattern exhibits many of the features of neurotic repetition compulsion. Thus, it is often maladaptive and tends to be compulsive, inflexible, irrational and ultimately non-satisfying. There is a notable similarity between the descriptions of Type A individuals in the behavioural literature and narcissistic individuals in the psychoanalytic literature. It is postulated that Type A individuals may have a deficient self-representation. This psychodynamic formulation of Type A as a variant of pathological narcissism has implications for assessment, prevention and management. In particular, it may help discriminate a sub-group of high achievers who are neurotically motivated and have abnormally high arousal. Only this sub-group may be at increased risk of coronary pathology.

Compulsive Behavior↗
PubMed1987

Addictive personality factors.

This study was designed to compare mean scores obtained by alcoholics, compulsive gamblers, smokers, chronic joggers, and control subjects on six subfactors of the MacAndrew Alcoholism Scale. Results indicated that some MacAndrew factors may be more sensitive to additive pathology than others. Alcoholics emerged as the most pathological group, in terms of scores on the Cognitive Impairment, Social Maladjustment, and Risk Taking scales. Gamblers and smokers appeared to be distinctly different, more socially oriented addicts. Frequency of jogging was negatively related to measures of addiction but positively related to measures of compulsiveness.

Adult↗