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PubMed2002

A novel cognitive-behavioral approach for treatment-resistant drug dependence.

Despite the application of treatments that combine methadone administration, weekly counseling, and contingency reinforcement strategies, many opiate-dependent patients continue illicit drug use. In this controlled study we piloted a novel cognitive-behavioral treatment (CBT) designed to reduce illicit drug use among patients receiving methadone treatment. The treatment targeted the reduction of sensitivity to interoceptive cues associated with drug craving, and trained alternative responses to these cues. Patients (N = 23) were randomly assigned to either this novel CBT program or a program of increased counseling, such that the two programs of treatment were equated for therapist contact, assessment time, and contingency-reinforcement strategies. We found that, compared to a doubling of contact with their outpatient counselor, the new program was associated with significantly greater reductions in illicit drug use for women, but not for men. Reasons for differential performance by women and men and future directions for this new treatment are discussed.

Adult↗

PubMedDate not supplied

Discriminative stimulus effects of ethanol: lack of antagonism with N-methyl-D-aspartate and D-cycloserine.

Several drug discrimination studies reported that both competitive and uncompetitive NMDA receptor antagonists substituted for ethanol stimulus in rats. In the present study we examined if compounds that act as agonists at the NMDA receptor complex, D-cycloserine (a partial agonist at the glycine positive modulatory site) and N-methyl-D-aspartate (an agonist at the glutamate binding site), could antagonize the discriminative stimulus effects of ethanol. Rats were trained to discriminate between IP administered 1.0 g/kg of ethanol (10% v/v) and saline under a sweetened milk-reinforced fixed ratio 10 (FR10) schedule of reinforcement. When the animals met the discriminative criteria, antagonism tests were conducted with D-cycloserine (0.3-10.0 mg/kg, IP) and N-methyl-D-aspartate (15.0-60.0 mg/kg, IP). Neither D-cycloserine nor N-methyl-D-aspartate antagonized the ethanol-mediated discriminative stimulus effects. In addition, D-cycloserine (3.0-300.0 mg/kg, IP) did not substitute for ethanol. These results indicate that at least certain agonists at the NMDA receptor complex do not attenuate the ethanol interoceptive cue in the rat.

Alcohol Deterrents↗

PubMedDate not supplied

Heartbeat awareness and heart rate reactivity in anxiety sensitivity: a further investigation.

We examined the effects of anxiety sensitivity (AS) and arousal induction on heartbeat awareness and heart rate reactivity in a nonclinical undergraduate sample. Students were randomly selected from a larger screening sample to fill two groups (high and low AS; n = 15 per group) based on Anxiety Sensitivity Index (ASI) [Peterson, R. A., & Reiss, S. (1992). Anxiety Sensitivity Index manual (2nd ed. revised). Worthington, OH: International Diagnostic Systems] scores. Participants completed a mental arithmetic/spelling task to induce arousal. At two phases (i.e., baseline vs. stress), participants estimated their heart rates during specified intervals using a mental tracking paradigm. Actual heart rates were simultaneously measured. Although heart rate did increase significantly from baseline to stress phases, high and low AS groups did not differ in terms of heart rate reactivity to the stressor. As hypothesized, high AS individuals were more accurate in estimating their actual heart rate as compared to low AS individuals. Contrary to hypothesis, the AS group differences in accuracy of heartbeat estimations did not vary across baseline vs. stress phases. Interestingly, only low AS individuals provided heart rate estimates which were significantly lower than their actual heart rate readings. Although high and low AS individuals did not differ in actual heart rate, high AS individuals provided significantly higher heart rate estimates than low AS individuals. These results are consistent with the interoceptive sensitivity hypothesis. Implications of the greater heartbeat awareness of high AS individuals are discussed.

Adolescent↗

PubMed2001

The prognostic value of initial EDI scores in anorexia nervosa patients: a prospective follow-up study of 5--10 years. Eating Disorder Inventory.

AIM: To study in a prospective manner the long-term prognostic value of the initially recorded Eating Disorder Inventory (EDI) scores in anorexia nervosa (AN) patients. METHODS: The 5--10-year outcome of 26 consecutive malnourished AN patients was prospectively recorded according to the initial EDI score. We selected only patients with full 6-month assessments for more than 5 years (mean 8.5 years). Eating behavior, quality of life, autonomy and insight capacity were prospectively assessed by the Morgan-Russell scale and a semi-structured interview. At the end of follow-up, 13 patients recovered and the 13 others had a poor outcome. RESULTS: In monovariate analyses, high initial EDI total score (P <.0007) and high initial scores for perfectionism (P <.001), ineffectiveness (P <.002), interpersonal distrust (P <.004), interoceptive awareness (P <.03) and drive for thinness (P <.05) were significantly associated with a poor prognosis 5--10 years afterward. In a multivariate analysis, only high initial scores for perfectionism (F = 8.43; P = 0.008) and interpersonal distrust (F = 7.46; P = 0.012) were significantly associated with illness severity. DISCUSSION: High EDI total score and subscales for perfectionism and interpersonal distrust could predict a long-term severe outcome in AN.

Adult↗

PubMed1998

The discriminative stimulus properties of U50,488 and morphine are not shared by fedotozine.

Fedotozine is a kappa opioid receptor agonist having antinociceptive properties but devoid of diuretic effects. The aim of the study was to evaluate the discriminative stimulus effects of fedotozine at doses previously reported to produce maximal effects in in vivo assays measuring kappa-mediated analgesia. By using a two-lever drug discrimination task, two groups of rats were trained to discriminate either a 3 mg/kg i.p. dose of the kappa opioid agonist, U50,488, or a 5 mg/kg i.p. dose of the mu opioid agonist, morphine, from saline. Once trained, rats were used to conduct tests of stimulus generalization with morphine, U50,488 and fedotozine along with another kappa agonist, CI-977, and another mu agonist, fentanyl. The stimulus effect of U50,488 was shared by CI-977 but not by morphine. Conversely, the stimulus effect of morphine was shared by fentanyl but not by U50,488. Fedotozine (1-10 mg/kg) failed to substitute to either U50,488 or morphine. These results indicate that, when administered at doses fully effective in producing antinociception, the interoceptive stimulus effects of fedotozine, if any, can be distinguished from those produced by U50,488 and morphine.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed2003

Eye closure in darkness animates sensory systems.

Single subject and group analyses (n = 12) showed that the eyes-open and eyes-closed states in complete darkness considerably and consistently differ in the patterns of associated brain activation in fMRI. During nonchanging external stimulation, ocular motor and attentional systems were activated when the eyes were open; the visual, somatosensory, vestibular, and auditory systems were activated when the eyes were closed. These data suggest that there are two different states of mental activity: with the eyes closed, an "interoceptive" state characterized by imagination and multisensory activity and with the eyes open, an "exteroceptive" state characterized by attention and ocular motor activity. Our study also shows that the chosen baseline condition may have a considerable impact on activation patterns and on the interpretation of brain activation studies.

Adult↗

PubMed2002

Eating attitudes and the use of alcohol, tobacco, and exercise among male and female adolescents.

OBJECTIVES: To determine the differences between male and female adolescents in the associations of disturbed eating attitudes with the use of smoking, alcohol, and exercise. METHOD: Nonclinical adolescents-174 males and 157 females-completed the Eating Disorders Inventory (EDI) and a measure of engagement in the use of smoking, alcohol, and exercise. An analysis of variance (ANOVA) was used to determine the impact of Gender x Use of the behaviour upon eating and related attitudes. RESULTS: Gender and use of smoking and alcohol were each related to eating attitudes. However, in the case of exercise, there were strong interactions of the behaviour and gender. Women who exercised regularly had higher levels of restriction, body dissatisfaction, and interoceptive awareness, whereas men did not. CONCLUSIONS: It appears that men and women exercise for different reasons, in relation to their eating and related attitudes. It is possible that men exercise for positive goals (e.g., fitness), whereas women exercise to escape perceived negative consequences (e.g., weight gain). This is not the case for alcohol and tobacco use. These findings are discussed, and further research is proposed.

Journal Article↗

PubMed2003

Trends in eating disorder symptomatology in an outpatient clinic: 1988-1998.

Eating disorders treatment has been altered by changes in the health care system. In addition, there has been a major emphasis on prevention in recent years. Yet, there are few investigations of the effects of these changes on the severity of patients' symptomatology at intake. This study examined differences in symptoms among women who presented to an outpatient clinic between 1988 and 1998. Patients were divided into Cohort 1 (1988-1992) and Cohort 2 (1993-1998). Patients with anorexia nervosa (AN) in Cohort 2 had significantly lower body mass indices (BMIs) at intake. Moreover, a greater number of patients with AN in Cohort 2 had BMIs<or=15, suggesting severe malnourishment. Cohort 2 patients with bulimia nervosa obtained higher scores on the Interpersonal Distrust, Interoceptive Awareness, and Maturity Fears subscales of the Eating Disorder Inventory. There were no cohort differences in eating disorder duration, exercising, laxative or diuretic use, or self-induced vomiting. These results provide some evidence that the severity of eating symptomatology has increased in recent years.

Journal Article↗

PubMed1994

Course of multi-impulsive bulimia.

Thirty-two consecutively admitted females with bulimia nervosa (purging type) according to DSM-IV and additional impulsive behaviours (multi-impulsive bulimia (MIB)) and 32 age-matched female controls with DSM-IV bulimia nervosa (purging type) (uni-impulsive bulimia (UIB)) were assessed longitudinally on admission and at discharge following in-patient therapy and at a 2-year follow-up. Multi-impulsive bulimics were defined as presenting at least three of the six of the following impulsive behaviours in their life-time in addition to their bulimic symptoms at admission: (a) suicidal attempts, (b) severe autoaggression, (c) shop lifting (other than food), (d) alcohol abuse, (e) drug abuse, or (f) sexual promiscuity. Multi-impulsive bulimics were more frequently separated or divorced, had less schooling and held less-skilled jobs. Except for interoceptive awareness (EDI), which was more disturbed in multi-impulsive bulimics, there were no differences concerning scales measuring eating disturbances and related areas. Multi-impulsive bulimics showed more general psychopathology--anxiety, depression, anger and hostility, psychoticism--differed in several personality scales from uni-impulsive bulimics (e.g. increased excitability and anger/hostility) and had overall a less favourable course of illness. Multi-impulsive bulimics also received more in- and out-patient therapy previous to the index treatment and during the follow-up period. The data support the notion that 'multi-impulsive bulimia' or 'multi-impulsive disorder' should be classified as a distinct diagnostic group on axis I or that an 'Impulsive Personality Disorder' should be introduced on axis II. The development of more effective treatment for multi-impulsive bulimia is warranted.

Adult↗

PubMed1995

The relationship of partial syndrome eating disorders to anorexia nervosa and bulimia nervosa.

A variety of sociocultural, familial and individual features associated with the eating disorders were examined in subjects with full syndrome (FS) and partial syndrome (PS) eating disorders and in normal high school students. The EAT-26 was administered to 995 high school students. This was followed by individual interviews with those who scored in the symptomatic range. Fifty-one students with PS eating disorders, 57 students without eating disorders (normal controls) and 30 hospital patients with FS, anorexia nervosa or bulimia nervosa were compared on subscales of the Eating Disorder Inventory, the Diagnostic Survey for Eating Disorders and the Beck Depression Inventory. The three groups displayed statistically significant differences on dimensions of EDI subscales Ineffectiveness and Interoceptive Awareness and also with respect to depression, history of being overweight and past history of emotional problems, as well as having mothers with medical illnesses. On these characteristics, the FS subjects displayed higher levels than the PS subjects, who in turn were higher than the NC subjects. The PS subjects displayed elevations on Body Dissatisfaction (EDI subscale), past medical illnesses, and mother's over-concern with eating and weight. These data support a continuum model of the eating disorders, but a continuum of multiple associated features rather than of dieting.

Adolescent↗

PubMed2006

Discriminative stimulus properties of the selective norepinephrine reuptake inhibitor, reboxetine, in rats: a characterization with alpha/beta-adrenoceptor subtype selective ligands, antidepressants, and antagonists at neuropeptide receptors.

Although little information is available concerning discriminative stimulus (DS) properties of antidepressants, rats can be trained to recognize the selective norepinephrine (NE) reuptake inhibitor, reboxetine (2.5 mg/kg i.p.). By analogy to reboxetine (effective dose50, 1.1), 'full' (80%) substitution dose50 was obtained with the NE reuptake inhibitors, nisoxetine (4.9), nomifensine (0.5) and BW1555,U88 (1.0). Full substitution was also attained with the NE/serotonin (5-HT) reuptake inhibitors, S33005 (0.3), venlafaxine (4.8) and duloxetine (26.8), and the tricyclics, imipramine (2.5) and clomipramine (2.9). In contrast, the 5-HT reuptake inhibitors, citalopram, sertraline and paroxetine (all >2.5), and the 5-HT reuptake inhibitors/5-HT2 receptor antagonists, nefazodone and trazodone (both >10.0), did not substitute for reboxetine. The 'atypical' antidepressants, mirtazapine (>10.0) and mianserin (>2.5), similarly failed to substitute. DS properties of reboxetine were dose-dependently blocked by the alpha1-adrenoceptor (AR) antagonists, prazosin (inhibitory dose50, 0.3) and WB4101 (0.5), but resistant to the alpha2-AR antagonists, atipamezole (>0.63), idazoxan (>2.5) and RX821,002 (>0.08), and to the beta1-AR and beta2-AR antagonists, betaxolol (>2.5) and ICI118,551 (>10.0). Interestingly, the neurokinin-1 receptor antagonist, GR205,171, stereospecifically substituted for reboxetine (1.1) compared to its less active isomer, GR226,206 (>10.0). The corticotrophin-releasing factor-1 antagonists, DMP695 (>40), CP154,526 (>10.0) and SN003 (>40.0), and the melanin-concentrating hormone-1 antagonist, SNAP-7941 (>40.0), failed to substitute for reboxetine. In conclusion, DS properties of reboxetine are mimicked by antidepressants recognizing NE transporters, and require functionally intact alpha1-ARs for their expression. The neurokinin-1 antagonist, GR205,171, mimics the interoceptive properties of reboxetine, possibly reflecting its elevation of extracellular levels of NE in corticolimbic structures.

Adrenergic Uptake Inhibitors↗

PubMed1980

Demethyl analogues of psychoactive methoxyphenalkylamines: synthesis and serotonin receptor affinities.

Mono-O-demethylation of several 2,5-dimethoxyphenalkylamines increases their affinity for the serotonin receptors of the isolated rat fundus preparation. In several instances, demethylation of methoxyphenalkylamines results in compounds which produce an antagonism which is not of a competitive nature. With respect to 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM), demethylation of the 2-methoxy group alters affinity in a manner which parallels that observed upon demethylation of 5-methoxy-N,N-dimethyltryptamine. Using a discriminative stimulus paradigm, behavioral studies with rats reveal that the 2-hydroxy analogue, but not the 5-hydroxy analogue, of DOM produces effects (interoceptive cues) similar to those produced by 5-methoxy-N,N-dimethyltryptamine.

Amines↗

PubMed1999

Clozapine's antipsychotic effects do not depend on blockade of 5-HT3 receptors.

Sixteen known 5-HT3 receptor blockers, including clozapine, fully or partially reverse the inhibitory effect of 1 microM GABA on [35S]TBPS binding, indicating that they are also GABA(A) antagonists, some of them selective for subsets of GABA(A) receptors. The 5-HT3 receptor blocker, ondansetron, has been reported to produce some antipsychotic and anxiolytic effects. However, no antipsychotic effects have been reported for a large number of highly potent 5-HT3 receptor blockers. Like clozapine, ondansetron partially reverses the inhibitory effect of GABA on [35S]TBPS binding. Additivity experiments suggest that ten 5-HT3 receptor blockers tested at low concentrations preferentially block subtypes of GABA(A) receptors that are among those blocked by clozapine. Wiley and Porter (29) reported that MDL-72222, the most potent GABA(A) antagonist described here, partially generalizes (71%) with clozapine in rats trained to discriminate an interoceptive clozapine stimulus, but only at a dose that severely decreases responding. Tropisetron (ICS-205,930) exhibits both GABA-positive and GABA-negative effects. R-(+)-zacopride is 6-fold more potent than S-(-)-zacopride as a GABA(A) antagonist. We conclude that the observed antipsychotic and, possibly, anxiolytic effects of some 5-HT3 receptor blockers are due to selective antagonism of certain GABA(A) receptors, and not to blockade of 5-HT3 receptors. We speculate that the anxiolytic and sedative effects of clozapine and several other antipsychotic drugs may be due to selective blockade of alpha1beta2gamma2 GABA(A) receptors which are preferentially located on certain types of GABAergic interneurons (probably parvalbumin positive). Blockade of these receptors will increase the inhibitory output of these interneurons. So far, no highly potent GABA(A) antagonists with clozapine-like selectivity have been identified. Such compounds may exhibit improved clozapine-like antipsychotic activity.

Animals↗

PubMed1998

Cognitive-behavioral therapy for panic: effectiveness and limitations.

The cognitive model of panic and cognitive-behavioral therapy were evaluated. It was argued that the cognitive model is not clear about the definition of threat, and that panic is evoked by the fear of the dissolution of the self. Furthermore, panic attacks will not lead to panic disorder unless the individual is experiencing general anxiety and is concerned with his/her physical or mental state. Controlled studies have demonstrated that cognitive-behavioral therapy is superior to other treatments for panic--85% of patients are panic-free at posttreatment and improvements are maintained at follow-up. However, 26% of waiting-list controls are also panic-free making the net percentage of panic-free treated patients 59%. There is room for improvement in at least 50% of patients, and a substantial number of patients continue to take medication and seek additional treatment. There is a need to determine the essential components of cognitive-behavioral therapy. It was predicted that exposure will prove to be the most crucial component. Exposure to phobic situations and interoceptive cues should be extended to the underlying causes of panic disorder, such as concerns with identity and dependency needs.

Cognitive Behavioral Therapy↗

PubMed2003

The stress response in anorexia nervosa.

Patients with eating disorders have been found to have problems with Interoceptive Awareness. This study seeks to examine this issue in an experimental paradigm. In the present study, we investigated the hypothesis that, in addition to lowering a body's autonomic stress response, a state of starvation also lowers the psychological stress response. Results indicated that those with anorexia nervosa showed a muted physiology, but they did not show a complete denial of negative emotion. No relation was seen, however, between their affective and physiological responses to a stress task, which contrasted results found for the controls.

Adaptation, Psychological↗

PubMed1993

Personality and behavioral vulnerabilities associated with risk status for eating disorders in adolescent girls.

This article presents first-year cross-sectional findings from a study of the development of eating disorders. Adolescent female (N = 937) 7th through 10th graders completed measures that included information on personality, self-concept, eating patterns, and attitudes. A risk status score was calculated on the basis of comprehensive information regarding DSM-III-R eating disorders criteria and other weight and attitudinal data. All personality measures showed significant differences according to risk, based on subject classification into high, moderate, and mild risk status and comparison groups. Early puberty was not associated with increased risk. The strongest predictor variables for risk were body dissatisfaction, negative emotionality, and lack of interoceptive awareness. The possible diathesis of personality including temperamental factors in the later development of an eating disorder is discussed.

Adolescent↗

PubMed1989

The specific psychopathology of bulimia nervosa: a comparison with restrained and unrestrained (normal) eaters.

The hypothesis that patients with bulimia nervosa and restrained eaters exist on a simple continuum of psychopathology was tested in 60 Ss (20 bulimics, 20 restrained eaters, 20 unrestrained eaters). Regarding measures related to dieting behavior and physical appearance, the restrained eaters differed significantly from unrestrained eaters and were similar to bulimic patients except for level of psychopathology. The restrained eaters could not be distinguished from the unrestrained eaters with regard to measures representing interoceptive perception, depression, self-esteem, and fears about interpersonal relationships. On these traits, bulimic patients could be clearly distinguished from the normal Ss. The results support a 2-component model of the psychopathology of bulimia nervosa.

Adolescent↗

PubMed1992

Neural mechanisms of emotion.

When viewed from an evolutionary perspective, the neural mechanisms of emotion can be seen to be distributed across the brainstem, limbic, paralimbic, and neocortical regions. Descending and ascending connections among these levels are discussed in relation to three types of emotional processes: peripheral effects on patterned bodily responses, central effects on cognitive processing, and subjective emotional experience. Descending influences from the higher to the lower levels allow for an increasing coordination and flexibility of emotional responses, culminating in patterned activity across the peripheral endocrine, autonomic, and motor systems. Ascending influences from lower to higher levels provide preparatory modulation of cortical pathways, thus enabling perceptual and cognitive processing that is adaptive given the current emotional state. The bodily feelings of emotion are a function of cortical interoceptive sensory fields, activated by centrally generated signals or peripheral inputs from the body.

Adult↗