The use of chance-corrected agreement to diagnose canine compulsive disorder: an approach to behavioral diagnosis in the absence of a 'gold standard'.
This study assessed the diagnostic accuracy of formal diagnostic criteria for canine compulsive disorder (canine CD). Canine CD is a syndrome of abnormal behaviors that are believed to result from conflict or frustration. Differential diagnoses include normal conflict behavior and learned behavior. In studies of canine CD, confidence in the diagnosis comes with knowing the accuracy of the diagnostic method. This accuracy may be quantified as the chance-corrected agreement between the diagnostic method and a 'gold standard' diagnostic test. The present study examined the agreement between diagnoses of canine CD made by an expert (the 'gold standard') and by using formal diagnostic criteria. The owners of 84 dogs suspected of having CD received 2 telephone interviews. The first utilized a detailed, pre-tested questionnaire; a dog was then diagnosed with CD if the behavioral history met 7 diagnostic criteria. The second interview was given by a behavioral expert whose diagnosis was based on personal experience. The interviewers were blind to each other's diagnoses. The chance-corrected agreement between diagnoses was minimal (kappa = 0.02) and disagreement was associated with 3 of the formal criteria: a history of conflict or frustration, an increase in the number of contexts that elicit the behavior, and an increase in the daily frequency of the behavior. Reasons for the disagreement include the order of the interviews, response biases, the setting of the interviews, and, possibly, the diversity of the behaviors associated with canine CD. To the authors' knowledge, this type of study is the first in clinical ethology to address validation of the diagnostic method. The results indicate 3 developmental aspects of canine CD that should be examined in future work. (+info)
The relationship between repetitive behaviors and growth hormone response to sumatriptan challenge in adult autistic disorder.
Autism is heterogeneous with respect to clinical symptoms and etiology. To sort out this heterogeneity in autism, we investigated whether specific neurobiological markers vary in parallel to core symptomatology. Specifically, we assessed growth hormone response to the 5-HT 1d agonist, sumatriptan, and linked this measure of serotonergic function to the severity of repetitive behaviors in adult autistic patients. Eleven adult patients with autism or Asperger's disorder were randomized to single dose sumatriptan (6 mg SQ) and placebo challenges, separated by a one-week interval. In adult autistic disorders, severity of repetitive behaviors at baseline, as measured by YBOCS-compulsion score, significantly positively correlated with both peak delta growth hormone response and area under the curve growth hormone response to sumatriptan. Thus, the severity of a specific behavioral dimension in autism (repetitive behaviors) parallels the sensitivity of the 5-HT 1d receptor, as manifest by sumatriptan elicited GH response. (+info)
Addiction, a disease of compulsion and drive: involvement of the orbitofrontal cortex.
Understanding the changes in the brain which occur in the transition from normal to addictive behavior has major implications in public health. Here we postulate that while reward circuits (nucleus accumbens, amygdala), which have been central to theories of drug addiction, may be crucial to initiate drug self-administration, the addictive state also involves disruption of circuits involved with compulsive behaviors and with drive. We postulate that intermittent dopaminergic activation of reward circuits secondary to drug self-administration leads to dysfunction of the orbitofrontal cortex via the striato-thalamo-orbitofrontal circuit. This is supported by imaging studies showing that in drug abusers studied during protracted withdrawal, the orbitofrontal cortex is hypoactive in proportion to the levels of dopamine D2 receptors in the striatum. In contrast, when drug abusers are tested shortly after last cocaine use or during drug-induced craving, the orbitofrontal cortex is hypermetabolic in proportion to the intensity of the craving. Because the orbitofrontal cortex is involved with drive and with compulsive repetitive behaviors, its abnormal activation in the addicted subject could explain why compulsive drug self-administration occurs even with tolerance to the pleasurable drug effects and in the presence of adverse reactions. This model implies that pleasure per se is not enough to maintain compulsive drug administration in the drugaddicted subject and that drugs that could interfere with the activation of the striato-thalamo-orbitofrontal circuit could be beneficial in the treatment of drug addiction. (+info)
Effect of clomipramine on monoamine metabolites in the cerebrospinal fluid of behaviorally normal dogs.
The tricyclic antidepressant, clomipramine, is an effective treatment for canine compulsive disorder (canine CD). This disorder is a clinical syndrome of abnormal conflict behaviors and its pathophysiology is unknown. However, because clomipramine is an effective treatment, information about the drug's neurochemical effect could enhance the understanding of canine CD. The following experiment used 6 behaviorally normal dogs to assess the effect of clomipramine (3 mg/kg, q24h, PO) on the central turnover of 3 monoamines (serotonin, dopamine, and norepinephrine) as measured by the concentrations of their respective metabolites in cerebrospinal fluid (CSF). In a randomized, placebo-controlled, AB-BA crossover experiment, cisternal CSF was taken after 1, 2, 4, and 6 wk on each treatment. No effect of clomipramine was detected. This contrasts with human studies that have suggested that clomipramine affects the concentrations of monoamine metabolites in lumbar CSF. However, those papers do not address methodological assumptions, such as (i) metabolites in CSF originate only from the brain, and (ii) concentrations of metabolites in cisternal/lumbar CSF reflect the concentrations in local areas of the brain. Notwithstanding the small sample size, our results suggest that more localized sampling techniques (e.g. microdialysis) are needed when examining the effect of drugs on central monoamine metabolites. Clomipramine's efficacy for canine CD indicates the need for neurobiological research and, to our knowledge, our study is the first of its kind in dogs. The resulting data are preliminary but they can inform optimal neurobiological studies of canine CD. (+info)
Compulsive Spitting, as a culture bound symptom has not been previously reported in the literature. Of 26 cases described, 8 were suffering from schizophrenia followed by 5 cases having mania, 4 each with depression and OCD, 3 with tic disorder and 2 with seizure disorder. More studies are warranted to study and report the culture bound symptoms in india and other countries. (+info)
Exposure-based treatment to control excessive blood glucose monitoring.
We investigated an exposure-based procedure for reducing excessive checking of blood glucose by a child with diabetes. In a changing criterion design, an exposure-based procedure was implemented by systematically exposing the child to decreasing amounts of information about blood sugar levels (checking) and thereby increasing exposure to potential hypoglycemia. Access to information was reduced in graduated increments, with the parents setting criteria to levels at which they were willing to adhere. Results demonstrated that the procedure was effective in reducing excessive blood glucose checking and in improving metabolic control. (+info)
Baclofen efficacy in reducing alcohol craving and intake: a preliminary double-blind randomized controlled study.
AIMS: The gamma-aminobutyric acid (GABA(B)) receptor agonist, baclofen, has recently been shown to reduce alcohol intake in alcohol-preferring rats and alcohol consumption and craving for alcohol in an open study in humans. The present study was aimed at providing a first evaluation of the efficacy of baclofen in inducing and maintaining abstinence and reducing craving for alcohol in alcohol-dependent patients in a double-blind placebo-controlled design. METHODS: A total of 39 alcohol-dependent patients were consecutively enrolled in the study. After 12-24 h of abstinence from alcohol, patients were randomly divided into two groups. Twenty patients were treated with baclofen and 19 with placebo. Drug and placebo were orally administered for 30 consecutive days. Baclofen was administered at the dose of 15 mg/day for the first 3 days and 30 mg/day for the subsequent 27 days, divided into three daily doses. Patients were monitored as out-patients on a weekly basis. At each visit alcohol intake, abstinence from alcohol, alcohol craving and changes in affective disorders were evaluated. RESULTS: A higher percentage of subjects totally abstinent from alcohol and a higher number of cumulative abstinence days throughout the study period were found in the baclofen, compared to the placebo, group. A decrease in the obsessive and compulsive components of craving was found in the baclofen compared to the placebo group; likewise, alcohol intake was reduced in the baclofen group. A decrease in state anxiety was found in the baclofen compared to the placebo group. No significant difference was found between the two groups in terms of current depressive symptoms. Baclofen proved to be easily manageable and no patient discontinued treatment due to the presence of side-effects. No patient was affected by craving for the drug and/or drug abuse. CONCLUSIONS: Baclofen proved to be effective in inducing abstinence from alcohol and reducing alcohol craving and consumption in alcoholics. With the limits posed by the small number of subjects involved, the results of this preliminary double-blind study suggest that baclofen may represent a potentially useful drug in the treatment of alcohol-dependent patients and thus merits further investigations. (+info)
Drug addiction and its underlying neurobiological basis: neuroimaging evidence for the involvement of the frontal cortex.
OBJECTIVE: Studies of the neurobiological processes underlying drug addiction primarily have focused on limbic subcortical structures. Here the authors evaluated the role of frontal cortical structures in drug addiction. METHOD: An integrated model of drug addiction that encompasses intoxication, bingeing, withdrawal, and craving is proposed. This model and findings from neuroimaging studies on the behavioral, cognitive, and emotional processes that are at the core of drug addiction were used to analyze the involvement of frontal structures in drug addiction. RESULTS: The orbitofrontal cortex and the anterior cingulate gyrus, which are regions neuroanatomically connected with limbic structures, are the frontal cortical areas most frequently implicated in drug addiction. They are activated in addicted subjects during intoxication, craving, and bingeing, and they are deactivated during withdrawal. These regions are also involved in higher-order cognitive and motivational functions, such as the ability to track, update, and modulate the salience of a reinforcer as a function of context and expectation and the ability to control and inhibit prepotent responses. CONCLUSIONS: These results imply that addiction connotes cortically regulated cognitive and emotional processes, which result in the overvaluing of drug reinforcers, the undervaluing of alternative reinforcers, and deficits in inhibitory control for drug responses. These changes in addiction, which the authors call I-RISA (impaired response inhibition and salience attribution), expand the traditional concepts of drug dependence that emphasize limbic-regulated responses to pleasure and reward. (+info)