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PubMed2003

Reduced response-inhibition in obsessive-compulsive disorder measured with topographic evoked potential mapping.

Recent neuroimaging studies have suggested that a hyperactivity of the frontal-striate neuronal circuits, including the orbitofrontal cortex and the basal ganglia, mediates the symptomatology of obsessive-compulsive disorder (OCD). However, there is also some evidence that the superior frontal cortex is less activated in OCD, and this local hypoactivity has been shown to be negatively associated with the symptomatology. As the superior frontal cortex is believed to be involved in inhibitory control, this study investigated the brain electrical activity during response inhibition in OCD. Twelve patients with OCD and 12 healthy controls performed a cued Go-NoGo task (continuous performance test), while event-related potentials were registered with 21 electrodes. Patients reacted significantly faster than controls, but did not differ from controls regarding the error rate. As a main result, we found a reduced frontal activity during the NoGo condition in OCD, which was condensed in a reduced anteriorisation of the brain electrical field. We suggest that this inhibitory deficit in OCD has a major contribution to the pathophysiology of OCD, which is underscored by the fact that the anteriorisation during the NoGo condition (NGA) was negatively correlated with the symptomatology as measured by the Yale-Brown Obsessive-Compulsive Scale.

Adult↗
PubMed1997

Hemispheric functional imbalance in a sub-clinical obsessive-compulsive sample assessed by the Continuous Performance Test, Identical Pairs version.

Obsessive-compulsive disorder (OCD) sufferers have long been observed to give excessive consideration to normally ignored exogenous and endogenous stimuli. This over-focused attention concerning their symptoms has led researchers to experimentally investigate the attentional mechanisms involved in this disorder and its psychobiological basis. Previous psychometric and neuropsychological research has demonstrated the validity of the sub-clinical analogue in the study of the mechanisms underlying OCD. In this study, 71 introductory university students were recruited from an original pool of 450 people on the basis of their scores on the Spanish version of the Padua Inventory. A high obsessive group (n = 35) was compared with a control group (n = 36) on a standard sustained attention task: the Continuous Performance Test, Identical Pairs version (CPT-IP). The results showed a significant interaction effect between CPT-IP subscales (verbal and spatial) and group membership. This effect was more evident among men. The results were unrelated to general intelligence, depression, anxiety, personality or motivational factors. These findings support the hypothesis that neuropsychological deficits in OCD may be related to a hemispheric functional imbalance rather than to a lateralised dysfunction of a particular hemisphere.

Adolescent↗
PubMed1998

5HT2C CYS23/SER23 polymorphism is not associated with obsessive-compulsive disorder.

A great deal of evidence suggests that a genetic component underlies obsessive-compulsive disorder (OCD). The response to serotonergic medications and the worsening of obsessive symptoms after administration of serotonergic agonists indicate that serotonergic mechanisms are involved in OCD. We investigated the role of the Cys23Ser mutation of the 5HT2C receptor gene in the etiology of this disorder by performing an association study comparing a sample of 109 OCD patients with a sample of 107 healthy control subjects. No allelic or genotypic association of OCD with the 5HT2C receptor gene mutation was revealed in our data. We also extended the association analysis to a subsample of 39 OCD patients that had previously been submitted to a challenge test with clomipramine. In the subsample of OCD patients that received the challenge with clomipramine, no association between the 5HT2C receptor gene mutation and response to the challenge test was found. Our results exclude any specific role of the Cys23Ser mutation of 5HT2C receptor gene in the etiology of OCD: it seems probable that more complex genetic models are needed to explain the involvement of serotonergic elements in the etiology of this disorder.

Adult↗
PubMed1998

Frontal lobe dysfunction in obsessive-compulsive disorder and major depression: a clinical-neuropsychological study.

Neuropsychological findings support a hypothesized relationship between obsessive-compulsive disorder (OCD) and the frontal lobe. The aim of the present study was to compare findings of neuropsychological tests of frontal lobe function in 28 OCD patients and 29 patients with major depressive disorder (MDD), all diagnosed according to DSM III-R criteria. The patient groups were homogeneous for educational level, handedness, duration of illness, and sex distribution. All 57 subjects received a battery of tests sensitive to frontal lobe dysfunction as well as the Wechsler Memory Scale (WMS). Clinical symptomatology in the MDD and OCD groups was assessed with the Hamilton Rating Scale for Depression and the Yale-Brown Obsessive-Compulsive Scale, respectively. The only significant difference between the two diagnostic groups for any of the neuropsychological indices, with age as a covariate, was in the Object Alternation Test, in which OCD patients had a significantly higher number of perseverative responses. Test performances were not correlated with clinical symptomatology or severity of illness. Our preliminary results confirm the hypothesis that there is a selective impairment of orbito-frontal cortex in OCD and seem to exclude the existence of specific frontal lobe dysfunction in MDD, even though the two disorders show clinical similarities.

Adult↗
PubMed1998

Nocturnal polysomnography in obsessive-compulsive disorder.

To determine if sleep abnormalities occur in obsessive-compulsive disorder (OCD), 2 nights of sleep electroencephalographic (EEG) recordings were obtained from 13 medication-free outpatients with OCD and 13 age- and sex-matched normal volunteers. Patients were awake more on night 2 than on night 1, whereas control subjects had less time awake on night 1; no other differences between groups were found on sleep latency, sleep time, minutes of movement, sleep efficiency, rapid eye movement (REM) latency or amount of stage 1, 2, 3, or 4 or REM sleep. Within the patient group, total scores on the Yale-Brown Obsessive-Compulsive Scale were negatively correlated with total sleep time (r = -0.51, P = 0.07), sleep efficiency (r = -0.51, P= 0.07), and duration of stage 1 + 2 sleep (r = - 0.49, P = 0.09) but not with REM time (r = - 0.05, P = 0.87) or latency (r = -0.26, P = 0.39). Previous sleep studies in OCD have had divergent results, especially regarding REM latency; our results suggest that many OCD patients have essentially normal sleep EEG findings.

Adult↗
PubMed2000

Perceptual alternation in obsessive compulsive disorder--implications for a role of the cortico-striatal circuitry in mediating awareness.

Mounting evidence suggests that obsessive compulsive disorder (OCD) results from functional aberrations of the fronto-striatal circuitry. However, empirical studies of the behavioral manifestations of OCD have been relatively lacking. The present study employs a behavioral task that allows a quantitative measure of how alternative percepts are formed from one moment to another, a process mimicking the brain state in which different thoughts and imageries compete for access to awareness. Eighteen patients with OCD, 12 with generalized anxiety disorder, and 18 normal subjects participated in the experiment, in which they viewed one of the three Schröder staircases and responded by pressing a key to each perceptual reversal. The results demonstrate that the patients with OCD have a higher perceptual alternation rate than the normal controls. Moreover, the frequency of perceptual alternation is significantly correlated with the Yale-Brown obsessive compulsive and the Hamilton anxiety scores. The increase in the frequency of perceptual reversals cannot easily be accounted for by learning or by different patterns of eye fixations on the task. These results provide further evidence that an impairment of the inhibitory function of the cortico-striatal circuitry might underlie the etiology of OCD. The implications of the results for a general role of the cortico-striatal circuitry in mediating awareness are discussed.

Adult↗
PubMed2000

Neuroanatomically based approaches to obsessive-compulsive disorder. Neurosurgery and transcranial magnetic stimulation.

Obsessive-compulsive disorder is a severe condition. Unfortunately, current medication and behavior therapies fail to adequately benefit some patients most severely affected. Advancing knowledge of brain circuit involvement has potential treatment implications. The neurosurgical techniques most often used in the United States for crippling, treatment-refractory obsessive-compulsive disorder are reviewed in the context of anatomic models of the illness. The use of transcranial magnetic stimulation to probe possible neuroanatomic and neurophysiologic substrates of this disorder is considered, and how the knowledge gained from such studies might advance treatment is presented.

Brain↗
PubMed1999

Tourette's and comorbid syndromes: obsessive compulsive and attention deficit hyperactivity disorder. A common etiology?

Tourette's syndrome (TS), a neuropsychiatric movement disorder that manifests itself in childhood, is often associated with comorbid symptomatology, such as obsessions, compulsions, hyperactivity, distractibility, and impulsivity. Epidemiological studies suggest that a substantial number of TS patients develop clinical levels of obsessive-compulsive disorder (OCD) and/or attention deficit hyperactivity disorder (ADHD). This review aims to provide an integrated account of the three disorders in terms of their comorbidity. Neuroimaging studies suggest that all three disorders involve neuropathology of the basal-ganglia thalamocortical (BGTC) pathways: TS in the sensorimotor and limbic BGTC circuits; OCD in the prefrontal and limbic BGTC pathways; and ADHD in the sensorimotor, orbitofrontal, and limbic BGTC circuits. The pattern of comorbidity and other evidence indicates that the TS gene(s) may be responsible for a spectrum of disorders, including OCD and ADHD, but also that the disorders OCD and ADHD can exist in their own right with their own etiologies.

Attention Deficit Disorder with Hyperactivity↗
PubMed2003

Obsessive-compulsive symptoms induced by atypical antipsychotics. A review of the reported cases.

Atypical antipsychotics (APs) are now widely in use in clinical practice. They exert a beneficial effect in patients with schizophrenic disorders, including cases resistant to traditional APs and negative symptoms. They have also enhanced the ratio of therapeutic efficacy to adverse effects. Atypical APs, mainly risperidone and olanzapine, have been used as adjunctive treatment in (selective) serotonin reuptake inhibitor [(S)SRI]-refractory cases with obsessive symptoms. However, de novo emergence or exacerbation of obsessive-compulsive (OC) symptoms during treatment with clozapine, risperidone, olanzapine and quetiapine has been described in the literature. The reported cases and the possible pathogenetic mechanisms involved in their occurrence are discussed and reviewed.

Antipsychotic Agents↗
PubMed2003

Olanzapine augmentation of paroxetine-refractory obsessive-compulsive disorder.

The aim of the present study was to investigate the effect of adjunctive olanzapine in patients with obsessive-compulsive disorder (OCD) refractory to paroxetine. Twenty-one patients unresponsive to treatment with paroxetine, administered for at least 12 weeks at the dose of 60 mg/day, participated to a 12-week open-label, add-on trial with olanzapine (10 mg/day). The psychopathological state was evaluated by the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and by Clinical Global Impression (CGI). Three patients did not complete the 12-week adjunctive treatment with olanzapine. In the 18 completers, the mean Y-BOCS score decreased significantly from 27.1+/-4.0 at baseline to 20.1+/-3.9 at final evaluation (P<.001). Seven patients (38.9%) were rated as responders at final evaluation. Steady-state plasma concentrations of paroxetine were not modified during olanzapine coadministration. The drug combination was generally well tolerated and initial sedation and weight gain were the most frequent unwanted effects. Our findings confirm the results of previous studies and indicate that the addition of olanzapine to ongoing treatment with serotonin reuptake inhibitors (SRI) may be beneficial in some patients unresponsive to SRI monotherapy.

Adult↗
PubMed1998

Brainstem involvement in obsessive-compulsive disorder.

We investigated the possible involvement of the brainstem in the pathology of obsessive-compulsive disorder. Brainstem auditory evoked potentials (BAEPs) were collected from a population of neurotics (100 patients), including a group of 50 subjects suffering from obsessive-compulsive disorder (OCD) and the rest having generalized anxiety disorder. Twenty-five, age- and sex-matched, healthy volunteers served as controls. BAEPs were recorded by standard techniques as recommended by the AEEGS Clinical Evoked Potentials Guidelines. A one-way analysis of variance and the Fisher least-significant difference test were used for statistical analysis of the data. After stimulation of the right ear, a significant increase of wave I-V interpeak latency was found in the two groups of patients as compared with that of controls. Moreover OCD patients had a significantly reduced amplitude of wave III when compared to that of the control group. Our electrophysiological data suggest a possible involvement of brainstem in OCD pathogenesis. We discuss our findings in relation to biochemical, anatomical and physiological alterations described in the literature for serotonin-dependent systems.

Adult↗
PubMed1999

Possible role of neuropeptides in obsessive compulsive disorder.

The most consistent finding in clinical research of obsessive compulsive disorder (OCD) is the significant treatment advantage of potent serotonin uptake inhibitors (SUIs) over other classes of antidepressant and antianxiety drugs. Clinical neurobiological studies of OCD, however, have yielded limited and inconsistent evidence for significant fundamental abnormalities in monoamine systems including serotonin, norepinephrine and dopamine. Furthermore, one-third to one-half of OCD patients do not experience a clinically meaningful improvement with SUI treatment. Investigation beyond the monoamine systems may be necessary in order to more fully understand the pathophysiology of obsessive-compulsive symptoms and develop improved treatments. Evidence from preclinical studies suggests that neuropeptides may have important influences on memory acquisition, maintenance and retrieval; grooming, maternal, sexual and aggressive behavior; fixed action patterns; and stereotyped behavior; these phenomena may relate to some features of OCD. In addition, extensive interactions have been identified in the brain between neuropeptidergic and monoaminergic systems, including co-localization among specific populations of neurons. The purpose of this review is to present the current knowledge of the role of neuropeptides in the clinical neurobiology of children, adolescents and adults with OCD focusing primarily on results from pharmacological challenge and cerebrospinal fluid studies. Where evidence exists, developmentally regulated differences in neuropeptide function between children and adolescents versus adults with OCD will be emphasized; these data are intended to underscore the potential importance of establishing the age of symptom onset (childhood versus adult) in individual patients with OCD participating in clinical neurobiological investigations. Likewise, where information is available, differences in measures of neuropeptides between patients with non-tic-related OCD versus tic-related OCD will be highlighted; these data will demonstrate the critical value of diagnostic precision, as these two particular subtypes of OCD may have different neurochemical underpinnings.

Adolescent↗
PubMed1997

Tourette syndrome. Medical and surgical treatment of obsessive-compulsive disorder.

Current treatment outcomes for obsessive-compulsive disorder patients are far better than in past decades, but variability in treatment response remains. Most obsessive-compulsive disorder patients, but not all, respond to antidepressant agents with prominent serotonin uptake blocking properties. Because clomipramine's usefulness is limited by side effects which often accompany its use, a considerable degree of attention has shifted to selective serotonin reuptake inhibitors. A number of studies have also provided evidence for the effectiveness of medication other than those mainly involving serotonergic function, either as augmenting agents or for comorbid disorders. Neurosurgery may be useful for highly selected subjects.

Brain↗
PubMed2000

Recurrent detoxification may elevate alcohol craving as measured by the Obsessive Compulsive Drinking scale.

Research has demonstrated a relationship between the number of previous alcohol detoxifications and increased severity of the alcohol withdrawal syndrome (AWS) that is hypothesized to be similar to an electrophysiologic "kindling process." Application of a "kindling" model to AWS suggests that neuroadaptation of the central nervous system to repeated detoxifications may also cause neurobehavioral alterations that may affect "craving." This study examined craving as assessed by the Obsessive Compulsive Drinking Scale (OCDS) in 67 adult outpatients meeting DSM-IV criteria (American Psychiatric Association, 1994) for alcohol dependence and AWS having either < 2 and > or = 2 previous detoxifications. Results of ANCOVA revealed that patients with > or = 2 previous detoxifications had higher scores on a scale that measures obsessive thoughts about alcohol, drinking urges and behaviors, and a composite of these scores after controlling for alcohol dependence severity, depressive symptoms and number of drinks 2 weeks prior to the study. Findings emphasize the need to address craving and other psychological variables with respect to treatment of AWS.

Adult↗
PubMedDate not supplied

Childhood obsessive-compulsive disorder in the NIMH MECA study: parent versus child identification of cases. Methods for the Epidemiology of Child and Adolescent Mental Disorders.

Abstract-Because as many as 50% of obsessive-compulsive disorder (OCD) cases have had onset by age 15, interest in its detection in childhood is strong. Clinical experience indicates that children often try to keep their OCD secret and that parental report may give marked underestimates. The authors examined the prevalence of childhood OCD in the NIMH Methods for the Epidemiology of Child and Adolescent Mental Disorders (MECA) Study, a four-site community survey which allowed comparison of both parent and child report of the child's OCD and related symptoms and disorders. OCD cases, based on structured interviews (DISC-2.3 with DSM-III-R criteria) with 1,285 caretaker-child pairs, were identified separately for parent and child (aged 9 through 17) informants from the MECA database. Cases were then examined for demographic characteristics, for obsessive-compulsive symptoms and other diagnoses reported in cases "missed" by one reporter, and for comorbid disorders. Of a total of 35 (2.7%) identified cases, four (0.3%) were identified by the parent and 32 (2.5%) were identified by the child, with only one overlapping case. In general, when OCD cases were "missed" by one reporter, that reporter did not substitute another disorder. These findings support clinical data that children with OCD often hide their illness and underscore the importance of child interviews for its detection.

Adolescent↗
PubMedDate not supplied

Inflated perception of responsibility for harm in obsessive-compulsive disorder.

The present study examined the proposition that inflated responsibility is implicated in obsessive compulsive disorder (OCD). Compared to non-anxious control participants (NACs), and an anxious control group with generalized social phobia (GSPs), we predicted that individuals with OCD (OCs) would exhibit a greater urge to rectify situations involving potential risk, would report more distress upon leaving such situations unrectified, and would feel more personal responsibility if the unrectified situations resulted in harm. Fifteen OCs, 15 NACs, and 15 GSPs completed the Obsessive Compulsive Responsibility Scale (OCRS), which included low-risk, OC-relevant, and high-risk situations. Compared to NACs and GSPs, OCs reported more urges, distress, and responsibility in low-risk and OC-relevant situations; no group differences were detected on high-risk situations. GSPs and NACs differed only in their responsibility in OC-relevant situations, with GSPs reporting higher responsibility than controls. Our results suggest that compared to OCs, NACs, and GSPs can better differentiate between situations that merit concern and ones that do not.

Adult↗
PubMed2002

Open trial of cognitive behavior therapy for childhood obsessive-compulsive disorder.

Examined the utility of CBT for childhood obsessive-compulsive disorder (OCD) including a preliminary exploration of predictors of response to this form of treatment. A total of 42 youngsters (mean age 11.8 years, 60% female, 52% on medication at baseline) with DSM-IV OCD were treated openly using a developmentally sensitive treatment protocol based on exposure plus response prevention (ERP). The treatment response rate (CGI < 2) was 79% with a mean decrease from baseline in NIMH global scores of 45%. Response was not related to age, gender, baseline medication status, comorbid symptomatology, or therapist experience. Poorer outcome was associated with more severe obsessions and greater OCD-related academic impairment at baseline. When presented in a developmentally appropriate manner, CBT is a useful treatment for childhood OCD. Controlled trials are needed to provide a more rigorous test of this treatment approach and provide better information regarding potential mediators and moderators of outcome.

Adolescent↗
PubMed2003

Further investigation of the obsessive-compulsive inventory: psychometric analysis in two non-clinical samples.

The obsessive-compulsive inventory [OCI; Psychol. Assessment 10 (1998) 206-214] is a self-report measure of obsessive-compulsive disorder (OCD) intended for use with both clinical and non-clinical samples (). Two reports support its convergence with established measures of OCD and its assessment of specific symptom subtypes (e.g., checking and washing). The current studies investigate the OCI factor structure in two non-clinical samples. Based on correlational analyses and complementary factor analyses, Study 1 results indicate that five subscales, rather than the seven rationally derived ones, best capture the structure of symptoms measured by the OCI. These findings were replicated in Study 2. Based on these analyses, we offer suggestions for revising the original subscales into these five empirically derived subscales that closely resemble structures proposed in the current OCD literature.

Adult↗