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PubMed2006

Role of atypical opiates in OCD. Experimental approach through the study of 5-HT(2A/C) receptor-mediated behavior.

RATIONALE: The selective serotonin (5-HT) reuptake inhibitors (SSRIs) represent the first-line pharmacotherapy for obsessive-compulsive disorder (OCD), and atypical antipsychotic drugs, which block 5-HT2A receptors, are used in augmentation strategies. Opiate drugs are also effective in treatment-refractory OCD and Tourette syndrome. The 5-HT2A-related behavior (i.e., head twitch) has been related with tics, stereotypes, and compulsive symptoms observed in Tourette syndrome and OCD. OBJECTIVES: The aim of this study was to explore whether 5-HT2A-related behavior is affected by atypical opiate drugs. MATERIALS AND METHODS: Head-twitch response was induced in mice by administration of either 5-hydroxytryptophan (5-HTP) or the 5-HT2A/C agonist (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI). Dose-effect curves of atypical opiate drugs [(+/-)-tramadol, (-)-methadone and levorphanol], morphine, and other psychoactive drugs (fluvoxamine, desipramine, nefazodone, and clozapine) were performed. Opioid mechanisms were investigated by administration of naloxone. RESULTS: All the opiates tested reduced both 5-HTP and DOI-induced behavior in a naloxone-reversible fashion, atypical opiates being more effective. The effects of the other drugs depended on the protocol, clozapine being the most effective. CONCLUSIONS: Combined 5-HT and opioid properties result in a greater efficacy in antagonizing 5-HT2A-related behavior. These results provide behavioral evidence to support convergent effects of the 5-HT and opioid systems in discrete brain areas, offering the potential for therapeutic advances in the management of refractory stereotypes and compulsive behaviors.

5-Hydroxytryptophan↗
PubMed2026

Advancements in the Understanding of the Genetics of Obsessive-Compulsive Disorder (OCD).

PURPOSE OF REVIEW: This review summarizes recent advances in the genetics of Obsessive-Compulsive Disorder (OCD), their contribution to understanding disorder biology, and implication for clinical translation. RECENT FINDINGS: Recent GWAS identified 30 genome-wide significant loci and prioritized 25 putatively causal genes. Rare variant studies implicated specific genes, including CHD8, CELSR3, SLITRK5, and QRICH1. Evidence from common and rare variants support brain- and immune-related pathways. Genetic overlap with obsessive compulsive symptoms and other psychiatric disorders indicate shared underlying biology. Current evidence is largely based on individuals of European ancestry, although global efforts are underway to improve ancestral diversity in OCD genetics. Given the urgent need for improved treatment, genetically informed clinical translation approaches hold promise, including pharmacogenetics and drug repurposing. Recent advances in OCD genetics support a highly polygenic architecture, implicate specific neuro-biological and immune pathways, and provide new opportunities for clinical translation.

Humans↗
PubMed2006

The hoarding dimension of OCD: psychological comorbidity and the five-factor personality model.

Although hoarding has been associated with several psychological disorders, it is most frequently linked to obsessive-compulsive disorder (OCD). The present study assessed hoarding obsessions and compulsions in 204 individuals with OCD, and evaluated how hoarding was related to obsessive-compulsive symptom severity, psychological comorbidity, and personality as measured by the five-factor model. Results indicated that hoarding in OCD is a dimensional variable that is positively associated with dysphoria, total number of lifetime Axis I disorders, and lifetime histories of bipolar I, PTSD, and body dysmorphic disorder. Hoarding was negatively correlated with the NEO-Personality Inventory-Revised (NEO-PI-R) factor of Conscientiousness and positively associated with the NEO-PI-R factor of Neuroticism. When all personality and psychopathology variables were entered into a regression equation, dysphoria, bipolar II disorder, Conscientiousness, age, and Extraversion emerged as significant predictors of hoarding severity. Recommendations are made for clinicians and for future research.

Adolescent↗
PubMed2004

Sympathetic magic in contamination-related OCD.

We examined whether patients with contamination-related obsessive-compulsive disorder (OCD) are characterized by sympathetic magic beliefs (i.e., an irrational understanding of how contagion is transmitted). We asked OCD patients (OCs), non-anxious control participants (NACs), and anxious control participants (ACs) to identify a "contaminated" object and rate its degree of contamination on a 0-100 scale. Next, we touched a clean pencil to the object, and participants rated the degree to which the pencil was contaminated. A second pencil was touched to the first pencil and was then rated. This process was continued for 12 pencils (12 degrees of removal from the original object). The same process was repeated using threat-non-relevant stimuli. Results indicated that for threat-relevant stimuli, OCs seemed to perceive a "chain of contagion" in which successive degrees of removal from the original object were not rated as less contaminated. In contrast, NACs and ACs quickly identified the pencils as not contaminated, suggesting that they recognize the contamination as degrading across objects. This difference was not seen using threat-nonrelevant stimuli. We also found that ratings of looming vulnerability (a belief that the contamination is spreading, approaching, or escalating in threat value) mediated the relationship between diagnostic group and the chain of contagion. We suggest that this process may be consistent with the sympathetic magic and disease-avoidance models of disgust, and that disgust may be a fruitful area for exploration in the study of OCD.

Adolescent↗
PubMed1999

Memory bias in obsessive-compulsive disorder (OCD).

There is a memory bias associated with depression, and good reason to expect a memory bias associated with anxiety. However, the results of studies reported to date have been ambiguous. Accordingly, an experiment was conducted to assess memory for contamination in people with different types of anxiety. Memory for contaminated stimuli among participants who met DSM-IV criteria for obsessive-compulsive disorder (OCD) and indicated a fear of contamination (n = 10) was compared to memory in a group of anxious controls (n = 10), and in undergraduate students (n = 20). Participants were shown 50 objects, 25 of which were contaminated by the experimenter and 25 which were touched but not contaminated. They then completed a neuropsychological memory assessment, after which the participants were asked to recall all of the objects touched by the experimenter. They were then asked to approach each object and to rate their anxiety about touching it. Finally, participants were asked about their perceptions of the cleanliness of each object. The OCD group had better memory for contaminated objects than for clean ones. Neither control group showed such a bias. Neuropsychological test scores indicated that this bias is not the result of differences in general memory ability. The results are discussed in terms of the memory-deficit theory of OCD and of behavioural and cognitive approaches to understanding the role of information processing in fear and anxiety.

Adult↗
PubMedDate not supplied

A placebo-controlled cross-over trial of adjunctive EPA in OCD.

Several clinical studies showed beneficial effects of omega-3 fatty acids in major affective disorders, including resistant depression. Some antidepressants are also effective, albeit less so, in obsessive-compulsive disorder (OCD). We therefore undertook a preliminary placebo-controlled cross-over trial of adjunctive eicosapentaenoic acid (EPA) in OCD. Eleven patients with current obsessive-compulsive disorder, who were on a stable maximally tolerated dose of SSRI with no further improvement over at least the last two months, were recruited. Subjects were randomly allocated to begin 6 weeks of placebo (2 g liquid paraffin per day) followed by 6 weeks of 2 g of EPA or EPA followed by placebo. Patients continued their prior SSRIs at the same dose. Assessments were performed with the Yale-Brown Obsessive-Compulsive Scale (YBOCS), and the Hamilton Rating Scales for depression (HAM-D) and anxiety (HAM-A). There were no effects of order of treatment. Time had a main effect of YBOCS scores; mean scores declined from 26.0 (+/-5) to 17.6 (+/-6) by week 6 on placebo and to 18.5 (+/-4) on EPA. There were no effects on HAM-D and HAM-A. No clinically relevant side effects were reported. The results of this study suggest that adjunctive EPA is ineffective against OCD.

Administration, Oral↗
PubMed2003

How to treat OCD in patients with Tourette syndrome.

Obsessive-compulsive disorder (OCD) constitutes an etiologically heterogeneous set of conditions, including a subtype that seems etiologically related to Tourette syndrome (TS). In order to treat OCD patients optimally, the clinician needs to integrate educational, psychological and pharmacological approaches. The most effective psychological intervention is cognitive-behavior therapy (CBT). Drug treatment includes clomipramine and all selective serotonin reuptake inhibitors (SSRIs). A subgroup of OCD patients, however, shows no significant improvement. Few studies suggest that the presence of tics is associated to a worse treatment response to SSRIs and that such patients benefit from combined therapy of serotonin-reuptake inhibitors plus neuroleptics. Independently of the presence of tics, there are several different augmentation strategies for resistant cases with drugs that interfere in the dopamine, serotonin, opioid and gonadal hormone systems. In addition, new therapies are now being tested against presumed postinfectious autoimmune processes. Finally, new developments are promising in neural circuit-based therapies, including neurosurgery for refractory patients.

Behavior Therapy↗
PubMed1999

Platelet [3H]paroxetine binding in patients with OCD-related disorders.

The recently introduced notion of clinical conditions being related one to another, the spectrum concept, permits the testing of the involvement of serotonergic systems in a broad range of disorders tentatively linked to obsessive-compulsive disorder (OCD) for which no pathophysiological hypotheses yet exist. We therefore compared the binding of [3H]paroxetine ([3H]Par), a ligand that specifically labels the serotonin (5-HT) transporter, in platelets of drug-free outpatients suffering from various OCD-related disorders with binding in platelets of OCD patients and healthy subjects. Diagnoses were made according to DSM-IV criteria. The most frequent diagnosis was that of body dysmorphic disorder, followed by impulse control disorder, kleptomania, Tourette's syndrome and trichotillomania. Platelet membranes and [3H]Par binding were studied according to standardized protocols. The results, showing a similarly decreased density of [3H]Par binding sites in both patient groups as compared with healthy subjects, suggest the presence of a shared abnormality at the level of the presynaptic 5-HT transporter, probably linked to a common dimension yet to be identified.

Adolescent↗
PubMed2003

Brain reactivity to specific symptom provocation indicates prospective therapeutic outcome in OCD.

A pertinent question in biological psychiatry is what differentiates responders and non-responders to pharmacological treatment. One possibility is that individual differences in the symptomatic spectrum as well as in the underlying biology of the disorder lead to the known 40% failure in pharmacological treatment. Our study aimed to maximize individual brain markers of obsessive-compulsive disorder (OCD) by applying single photon emission computed tomography (SPECT) during a provoked symptomatic state prior to and following treatment. Four brain SPECT scans were obtained from 26 OCD patients prior to and at 6 months of sertraline treatment. At each time point, two SPECT scans were performed in a counterbalanced order of two specific states; one a symptom-provoking condition and the other a relaxed condition. At 6 months of treatment, patients were divided into responders and non-responders according to a predetermined clinical criterion. Prospective responders showed significantly lower brain perfusion in the dorsal-caudal anterior cingulum and higher brain perfusion in the right caudate, when compared to non-responders, only during symptom provocation. When pre- and post-treatment scans during symptom provocation were compared, only responders showed significant change in brain response: increased perfusion in the left anterior temporal cortex and prefrontal cortex at 6 months' treatment. These findings suggest that obtaining functional brain imaging during specific symptom provocation emphasizes individual differences in brain reactivity. Thus can indicate prospective responders to symptom-related treatment in OCD and mark the relevant brain regions for effective response to treatment.

Adult↗
PubMed2002

[Behavioral Group Therapy for Patients with OCD and Family Members].

PROBLEM: Behavioral group therapy program is presented of patients with OCD and the involvement of their significant others. First experiences of evaluation are reported. METHOD: 20 patients (10 women, 10 men) diagnosed with OCD were treated in a 16-session behavioral group therapy which included the involvement of 17 family members in selected sessions. The behavioral group therapy program involved cognitive restructuring, behavior exposure to anxiety-evoking stimuli and the discussion about the family system. Y-BOCS and a self-rating scale for the assessment of treatment benefit were used as outcome measures. RESULTS: In this study, Y-BOCS scores reduced from a mean of 24 before therapy to 19,8 after therapy. Patients and their significant others agreed on the general benefit from the group therapy and the level of understanding of individual problems. Family members in particular appreciated that they had learned more about coping strategies regarding OCD-symptoms.The majority of patients and their significant others would recommend behavioral group therapy to other affected people. CONCLUSIONS: Behavioral group therapy can be effective in reducing OCD-symptoms. Inclusion of family members in behavioral group therapy may be advantageous, because they can assist the patients during their treatment. This form of treatment may become an attractive and cost-effective alternative to conventional group settings.

Adolescent↗
PubMed2005

Obsessive-compulsive disorder (OCD) with psychotic symptoms and response to treatment with SSRI.

The co-occurrence of obsessive-compulsive and psychotic symptoms in one patient often represents a diagnostic problem. Distinguishing among a schizophrenic disorder with comorbid obsessional symptoms, an OCD with comorbid psychotic symptoms, or an OCD and schizophrenia or any other psychotic disorder is of clinical importance, since the different diagnoses have different therapeutic as well as prognostic implications. In the following case report we describe a patient who suffered from a typical OCD for more than 18 years and then developed clear psychotic symptoms that completely remitted after treatment with citalopram.

Adult↗
PubMed2004

Conditional-associative learning in eating disorders: a comparison with OCD.

The acquisition of conditional associations using neutral and individually threatening verbal stimuli was assessed in 16 females with anorexia nervosa (AN), obsessive-compulsive disorder (OCD), bulimia nervosa and normal controls, respectively. Groups did not differ in terms of age, sex, intelligence, depression, verbal memory and verbal fluency measures. Patients and controls were widely comparable on tests assessing neuropsychological functioning. In the conditional-associative learning (CAL)-task only anorectic and OCD-patients displayed an impaired performance with neutral material but not with individually threatening material. Such a deficit was not evident in bulimics or in normal controls. These findings support the assumptions from functional neuroimaging investigations in AN and OCD and provide evidence that obsessive and compulsive behavior could have its origin within common neurobiological dysfunctions. The CAL possibly serves as a functional correlate of a neurophysiological dysfunction in obsessive-compulsive spectrum disorders.

Adolescent↗
PubMed2005

The role of cognitions in OCD treatment: toward rapprochement.

The authors of the papers in this special issue have underscored the efficacy of both psychological and pharmacological treatments for OCD. Despite the potency of these interventions, complete symptom remission rarely occurs. Furthermore, problems related to treatment drop-out, the persistence of residual symptoms despite adequate therapy, patients' vulnerability to relapse and recurrence, and the lack of a clear method for managing co-morbidity or treating OCD subtypes remain incompletely addressed. This response to the authors' papers evaluates their positions and extends their papers by examining issues such as how cognitive therapy and exposure and response prevention can best be integrated, the role of medication in OCD treatment, factors that impact treatment readiness and/or resistance, and the need for effectiveness research.

Adult↗
PubMed2001

Case study: caudate glutamatergic changes with paroxetine persist after medication discontinuation in pediatric OCD.

Proton magnetic resonance spectroscopy (1H-MRS) was used to examine glutamatergic (Glx) abnormalities in the caudate nucleus in pediatric obsessive-compulsive disorder (OCD), associated with severity of illness and response to acute (12 weeks) treatment with paroxetine. In this report, OCD symptoms improved markedly in an 8-year-old girl treated for 14 months with the selective serotonin reuptake inhibitor paroxetine (titrated from 10 to 40 mg/day). Paroxetine dose was then decreased in 10-mg decrements and discontinued without symptom recurrence. Serial 1H-MRS examinations were acquired before and after 12 weeks of paroxetine treatment (40 mg/day) and 3 months after medication discontinuation. A striking decrease in caudate Glx was observed after 12 weeks of treatment which persisted after medication discontinuation. These data provide further support for a reversible glutamatergically mediated dysfunction of the caudate nucleus in OCD that may serve as a pathophysiological and treatment response marker.

Brain Chemistry↗
PubMed2005

A right orbitofrontal region and OCD symptoms: a case report.

OBJECTIVE: To discuss the relationship between obsessive-compulsive symptoms and a right orbitofrontal lesion. METHOD: Single case report. RESULTS: A 59-year-old man developed obsessive-compulsive disorder (OCD) symptoms after his head injury. Magnetic resonance imaging brain scans showed a small contusion in the right orbitofrontal region, and single-photon emission computed tomography revealed hypoperfusion in blood flow at the same region. CONCLUSION: The OCD symptoms that developed in the present case may be attributable primarily to hypofunction in the lesion localized to the right orbitofrontal area. Although caution is needed for interpretation of the observation because of our experience of only a single case, it suggests that the right orbitofrontal region may be important in forming OCD symptoms.

Brain Concussion↗
PubMed2003

Buddhism, behavior change, and OCD.

For individuals with obsessive compulsive disorder (OCD), the difficulty of their situation comes as no surprise. But what might be less expected is how directly their situation is spoken to in Buddhist teachings. Still, in nearly all mainstream discussions of psychiatric disorders, including OCD, the rich philosophical and spiritual dimensions of these conditions and the related treatment and care tend to be either ignored or disguised in euphemisms and vague explanations. This article sheds light on this hidden aspect of psychiatry and psychiatric nursing through a philosophical analysis of one of the most popular approaches to treating OCD, Schwartz's four-step method from Brain Lock. In so doing, the argument is made that sharing the philosophical and spiritual foundations of treatment and care promises not only to deepen the insights and skills of clinicians but also to empower clients as participants in their own journeys toward wellness and beyond.

Attitude to Health↗
PubMed2001

Compulsive checking behavior of quinpirole-sensitized rats as an animal model of Obsessive-Compulsive Disorder(OCD): form and control.

BACKGROUND: A previous report showed that the open field behavior of rats sensitized to the dopamine agonist quinpirole satisfies 5 performance criteria for compulsive checking behavior. In an effort to extend the parallel between the drug-induced phenomenon and human obsessive-compulsive disorder (OCD), the present study investigated whether the checking behavior of quinpirole rats is subject to interruption, which is an attribute characteristic of OCD compulsions. For this purpose, the rat's home-cage was placed into the open field at the beginning or the middle of a 2-hr test. RESULTS: Introduction of the home-cage reduced checking behavior, as rats stayed inside the cage. After 40 min, checking resurfaced, as quinpirole rats exited the home-cage often. An unfamiliar cage had no such effects on quinpirole rats or saline controls. CONCLUSIONS: Checking behavior induced by quinpirole is not irrepressible but can be suspended. Results strengthen the quinpirole preparation as an animal model of OCD compulsive checking.

Animals↗
PubMed1997

Brain blood flow in anxiety disorders. OCD, panic disorder with agoraphobia, and post-traumatic stress disorder on 99mTcHMPAO single photon emission tomography (SPET).

BACKGROUND: We compared regional cerebral blood flow (rCBF) in three groups of patients with DSM-III-R anxiety disorders. METHOD: Fifteen patients with obsessive -compulsive disorder (OCD), 15 with panic disorder with agoraphobia (PA), and 16 with post-traumatic stress disorder (PTSD) and a similar group of healthy controls were assessed on brain-dedicated high-resolution SPET. RESULTS: MANOVA revealed significant rCBF differences between diagnostic groups (F = 4.4; d.f. = 3, 57; P = 0.007) and between cerebral regions (F = 6.4; d.f. = 1, 57; P = 0.01) in OCD and PTSD compared with PA and healthy controls, limited to bilateral superior frontal cortices and right caudate nuclei. Whole brain blood flow correlated positively with anxiety (r = 0.24, n = 46, P = 0.05). Beck depression scores correlated significantly negatively with left caudate rCBF (r = -0.24, n = 46, P = 0.05) and right caudate rCBF (r = -0.31, n = 46, P = 0.02). PTSD syndrome severity correlated significantly negatively with the left caudate (r = -0.49, n = 16, P = 0.03) and with right caudate rCBF (r = -0.7, n = 16, P = 0.001). CONCLUSIONS: Functional rCBF differences in anxiety disorders could relate to repetitive, intrusive, distressing mental activity, prominent in both OCD and PTSD.

Adult↗