[Treatment of obsessive and phobic states].
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BACKGROUND: Body dysmorphic disorder (preoccupation with an imagined or slight defect in appearance) is a common and disabling disorder associated with high rates of delusional symptoms and suicide attempts. Although preliminary studies suggest that serotonin reuptake inhibitors may be effective for body dysmorphic disorder, to date no controlled treatment studies have been published. METHODS: Forty patients were enrolled and 29 were randomized into a 16-week, double-blind, crossover-design study of clomipramine, a potent serotonin reuptake inhibitor, and active control desipramine, a selective norepinephrine reuptake inhibitor. Outcome measures included specific ratings of body dysmorphic disorder severity, delusionality, and functional impairment. RESULTS: Clomipramine was superior to desipramine in the acute treatment of body dysmorphic disorder symptoms as measured by assessment of patients' obsessive preoccupation with perceived body defects, repetitive behaviors in response to this preoccupation, and global ratings of symptom severity. Treatment efficacy was independent of the presence or severity of comorbid diagnoses of obsessive-compulsive disorder, depression, or social phobia. Likewise, clomipramine was equally effective regardless of whether the patients had insight or held their dysmorphic misperception with delusional intensity. Clomipramine was also superior to desipramine in improving functional disability. CONCLUSIONS: Clomipramine is more effective than desipramine in the treatment of body dysmorphic disorder and is effective even among those patients who are delusional.
Serotonin (5-HT), one of the evolutionary oldest central neurotransmitters, regulates the most extensive modulatory behavioral system in the brain of vertebrates. 5-HT projections are influenced by extrinsic and intrinsic impulses from different cortical brain areas, which reach Raphe nuclei over feedback loops, containing external and internal body information about planning, evaluation, motivation or excitation. Serotonergic neurotransmission adjusts neuromodulation with consecutive adequate stimulation of the neuronal network. This depends on appropriate equilibration of presynaptic 5-HT storage and release but also on 5-HT reuptake from synaptic cleft by 5-HT transporters. The associated pre and postsynaptic 5-HT receptor cooperation, postsynaptic second messenger response and phosphoinositide signaling mediated by postsynaptic 5-HT(2) receptor subpopulation alter signal transduction in which myristolated alanine rich C kinase substrate is prominently involved in regulation of further central 5-HT areas in the brain and corresponding functional neuronal changes. Even though the central function of 5-HT neurotransmission is dominating in the multifold behavioral regulation, peripheral concentration of tryptophan (TRP) adjusted by hepatic and non-hepatic TRP pyrrolase, TRP liberation from albumin especially by adrenergic stimulation of free fatty acids, TRP passage across the blood-brain barrier and TRP hydroxylase activity are also important for appropriate 5-HT neurotransmission as they affect central 5-HT synthesis. The high adaptability of 5-HT neurotransmission is able to compensate neuromodular dysfunctions in the brain by mechanisms which mediate 5-HT biosynthesis, release, reuptake, pre and postsynaptic receptor stimulation with the respective second messenger response and signal transduction to various areas of the brain which are involved in regulation of behavior, mood, memory, learning and attenuation of obsession, depending on the different vigilance states of the subject. Adequate 5-HT system function supports regulation of intercommunicative neuronal transmission in the brain, which optimizes behavioral neuromodulation during and after transient disturbances of neuromodular behavior caused by stress-induced exertions, but also in permanent disorder such as major depression. Serotonergic neurotransmission improves the clinical course due to compensatory 5-HT impulse correction. This hypothetical interpretation of the serotonergic central neuromodular regulation and interaction with the neuronal network is supported by findings both in functional disturbances and persistent impairments in mental disorders. A comparison of the symptomatology in permanent and transient disturbance of brain neuromodulation enhances our basic knowledge on the regulative factors e. g. in endogenous depression and depressive behavioral changes after exhaustive exercise. This consideration exhibits that the interaction between altered central neuromodulation and peripheral metabolic and hormonal dysfunctions is able to differentiate the etiology of the symptoms. It is suggested that the central neuromodular disturbance of stress-induced causes might initiate the manifestation of the impairment. The theoretical background of this hypothesis is discussed in the present review.
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Predictors of improvement in obsessive-compulsive symptoms (Y-BOCS) in a randomized clinical trial with adult obsessive-compulsive disorder outpatients were examined. Results of multiple regression analyses revealed that a positive helping alliance was significantly predictive of posttreatment Y-BOCS. Treatment expectancy and high motivation to change were not significantly related to posttreatment outcome. None of the predictors were significantly related to Y-BOCS levels at 12-month follow-up, but positive alliance showed a trend to significance.
This article discusses the presenting signs, diagnosis, and differential diagnosis of compulsive disorder. Problems with the diagnosis and heterogeneity of the condition are discussed. Likely causes, development, and pathophysiology of the condition form the basis for the clinical approach to the treatment of the condition. Treatment includes environmental and management changes, behavioral modification, and drugs.
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The antidepressants clomipramine hydrochloride (Anafranil), fluoxetine hydrochloride (Prozac), and sertraline hydrochloride (Zoloft) are the main choices for pharmacologic treatment of obsessive-compulsive disorder. Often, drug doses for obsessive-compulsive disorder are higher than for depression, and improvement occurs more slowly and is often only partial. Behavior therapy involving exposure to feared objects or situations and prevention of ritualistic behavior complements pharmacologic treatment. Referral to a behavioral therapist may be necessary to achieve recovery.
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OBJECTIVE: The aim was to describe the short-term (6 months) effects of olanzapine on behavioral and motor clinical manifestations in a group of 11 patients with Huntington disease. METHOD: An open-pilot study of olanzapine (5 mg) in patients with clinical and genetic diagnosis of Huntington disease was used. The Unified Huntington Disease Rating Scale for clinical assessment and the Total Functional Capacity score for the disease-stage evaluation were used. A statistical analysis was performed to compare the effects of olanzapine on the Unified Huntington Disease Rating Scale scores at time 0 (baseline) and at time 1 (6 months). Comparisons of motor scores, of single behavioral items, and of TFC scores were performed within the group. RESULTS: The behavioral assessment score of items regarding depression, anxiety, irritability, and obsessions showed a significant improvement (range of p, 0.0134-0.048). Given the total behavioral scores (sum of all the items investigated), five patients significantly improved their behavioral score after a 6-month treatment (range of p, 0.013-0.047). Choreic movements improved, although not significantly (0.05 < or = p < or = 1). CONCLUSIONS: Olanzapine is a potentially useful antipsychotic drug, with significant short-term effects on behavioral changes, mainly in patients with severe psychiatric symptoms at the onset. It might be considered as a possible therapeutic choice for treatment of Huntington disease.
The tic disorder Tourette's Syndrome (TS) and obsessive-compulsive disorder (OCD) are comorbid behavioral disorders, suggesting a shared but still unknown neuronal basis. To 'circuit-test' such behaviors, we previously engineered transgenic mice expressing a neuropotentiating protein (cholera toxin A1 subunit) within a cortical-limbic subset of dopamine D1-receptor expressing (D1+) neurons known to trigger glutamatergic excitation of orbitofrontal, sensorimotor, limbic and efferent striatal circuits thought to be hyperactive or affected in OCD and TS. These mice exhibited OCD-like behaviors including generalized behavioral perseveration and compulsion-like leaping and grooming-associated pulling and biting of skin and hair. We now report that these OCD-like mice, like humans, also exhibit comorbid TS-like behaviors, including juvenile-onset tics; increased tic number, complexity and flurries; increased tic severity in males; voluntary tic suppression; and tic responsiveness to a non-cataleptic TS+OCD drug therapy (clonidine, 0.01 mg kg(-1)). These data suggest that hormonal gender differences, apart from the influence of genetic or autoimmune etiologic factors, may be sufficient to aggravate tic severity in human TS males compared to TS females. These data also proffer a precise neuronal basis for TS+OCD, wherein tics and primary compulsions or obsessions are evoked by hyperactivity of various cortical-limbic projection neurons' glutamatergic output to efferent targets like the striatum. The 'Cortical-limbic Glutamatergic Neuron' (CGN) neuronal circuit model merges formerly opposed neurotransmitter models of TS and OCD, and is consistent with new clinical reports of increased cortical hyperactivity, striatal glutamate and striatal inhibitory D2 receptors, and reduced striatal responsiveness, in these disorders.
Under a psychoanalytic view, the etiological relevance of neurobiological modeis of obsessive-compulsive-disorder is discussed referring pharmacological and behavioral therapeutic options. From the beginnings of clinical psychoanalytic research, neurobiological correlates were considered for the understanding of obsessive-compulsive-disorder. However, within etiological psychoanalytic modeis those correlative biological markers have not the Status of monocausal independend variables. New biological findings regarding obsessive-compulsive-disorder can also be integrated in psychoanalytic concepts without renunciation of the significance of unconscious processes and an interaction oriented approach. Insight and Symptom oriented therapies are characterized with regard to necessary further research and to their complementary benefits.
The aim of this study is to derive a system of classification of compulsive phenomena occurring in obsessive compulsive disorder (OCD). 461 compulsions were found in 65.53% of 412 patients seen during the decade 1975 to 1984. An attempt has been made to break down the compulsions observed into different categories of form and content. The rationale for such a classification has been presented, and earlier attempts at classification of compulsions reviewed.
OBJECTIVE: The study examined the effectiveness of a partial hospital treatment program combining behavioral therapy, medication, and psychosocial intervention for severe and treatment-resistant obsessive-compulsive disorder. METHODS: A total of 58 patients with a primary diagnosis of obsessive-compulsive disorder who underwent treatment in a partial hospital program were assessed at baseline, at program discharge, and at six-, 12-, and 18-month follow-ups. Obsessive-compulsive symptoms, depression, anxiety symptoms, and global functioning were rated. RESULTS: The majority of patients (71 percent) met the criterion for a successful outcome, which was a 25 percent decrease in score on the Yale-Brown Obsessive Compulsive Scale (YBOCS). Fifty-five percent finished the program with YBOCS scores of 16 or less, indicating only mild symptoms. Most of these patients sustained their improvement at six, 12, and 18 months after discharge, and many showed further improvement with continued outpatient management. CONCLUSIONS: The partial hospital treatment program for obsessive-compulsive disorder appears to be an effective intervention that should be implemented and investigated further.
Hyperactivity is frequently observed in eating disorders, and several biopsychological mechanisms have been proposed to explain its pathogenetic role. In view of the lack of a reliable method to study hyperactive behavior, we did an experiment with experience sampling methodology (ESM). During 1 week, an anorexia nervosa (AN) patient was asked at nine random times a day to report her momentary tendency to be physically active, her emotions and several other variables including calorie expenditure, drive for thinness, attractiveness, obsessions, compulsions, and attitudes towards hyperactivity. Results indicate that the patient's tendency to be hyperactive was (a) positively related to her weight preoccupation and her negative emotions, and (b) negatively related to her positive emotions and the absence of depression. In this patient, obsessions and compulsions were not related to hyperactivity. The usefulness of ESM for studying the role of hyperactivity in AN is discussed.
Rats treated chronically with the dopamine D2/D3 receptor agonist quinpirole develop locomotor sensitization and exhibit compulsive checking of specific places in an open-field arena, a behavioral profile that may represent an animal model of obsessive-compulsive disorder. However, it is not known how compulsive checking develops across quinpirole injections nor whether checking behavior possesses a particular temporal structure. Male rats received quinpirole (0.5mg/kg, twice weekly x 10) or an equivalent regimen of saline and were placed in a large open field for 55 min where their behavior was digitally tracked for subsequent analysis of checking behavior using existing and newly developed computer software. Results showed that the measures of compulsive checking did not follow a singular profile across injections: some remained constant and others changed monotonically reaching their near-maximum levels after about 5-7 quinpirole injections. Moreover, results showed that checking behavior was organized into bouts of checking, with the number of bouts, as well as the rate of checking within a bout, increasing across injections to reach near maximal levels after about 5-7 administrations of quinpirole. Finally, quinpirole-treated rats showed a paucity of long inter-bout intervals. These results suggest that (a) compulsive checking emerges from the operation of at least two underlying processes: a regulated process and a process of sensitization that intensifies the performance of checking behavior; and (b) quinpirole treatment may attenuate a sense of satiety that could underlie the compulsive nature of checking. Finally, because key variables measured using the newly developed algorithms showed the expected profile, the present study provides validation for the use of this methodology for the analysis of checking behavior.
To date, few studies have examined the personality characteristics and clinical predictors of impulsive behaviors in eating disorders (ED). The aim of this work was to study the prevalence of a wide range of impulsive behaviors in a sample of 554 ED subjects and to examine the predictors of these behaviors. Subjects were diagnosed according to DSM-IV criteria as having anorexia nervosa restricting type (ANR; n = 183), anorexia nervosa binge eating/purging type (ANBP; n = 65), bulimia nervosa purging type (BNP; n = 244), and bulimia nervosa nonpurging type (BNNP; n = 62). Nine different types of impulsive behaviors were assessed in these groups. About 55% of the whole sample reported at least one type of impulsive behavior, 35% more than one, and about 13% more than three. According to findings, impulsive and multi-impulsive subjects are characterized by the presence of purging behavior and by specific temperamental features such as high levels of novelty seeking and low persistence. The prediction of impulsive behavior is further improved by considering the presence of a history of childhood abuse, maternal psychiatric morbidity, and some specific psychological symptoms such as maturity fears, perfectionism, depression, and obsessive-compulsive symptoms. The presence of impulsive behavior appears to be associated with overall higher levels of psychiatric symptomatology and eating psychopathology, thus indicating that they are an important feature to be considered in the assessment and treatment of ED.
Much of the existing literature examining the role of disgust is limited to specific phobia. Recent research has begun to examine the role of disgust in contamination fear, a subtype of obsessive-compulsive symptoms. Through the use of behavioral avoidance tasks (BATs), the current study was designed to examine the role of disgust in people with contamination fears, with attention to distinguishing high and low trait anxiety. From a large screening of undergraduate students, three groups were formed based on their level of contamination fear and level of trait anxiety: contamination fearful ( n = 12 ), high-trait anxiety ( n = 11 ), and low trait anxiety ( n = 15 ). Subjects were asked to engage in six different BATs corresponding to six domains of disgust (food, animals, body products, body envelope violations, death, and sympathetic magic). One-way analysis of variance (ANOVA) showed significant differences between the contamination fearful group and the high trait anxiety group on the animal and sympathetic magic BATs. Significant differences on the food, animal, body envelope violations, and death BATs were also found between the contamination fearful group and the low-trait anxious group. The findings modestly support the importance of disgust in contamination fears. Implications for the study of disgust in contamination fear are provided.