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PubMed2004

Early- versus late-onset obsessive-compulsive disorder: investigating genetic and clinical correlates.

There is increasing evidence that obsessive-compulsive disorder (OCD) is mediated by genetic factors. Although the precise mechanism of inheritance is unclear, recent evidence has pointed towards the involvement of the serotonergic and dopaminergic systems in the disorder's development. Furthermore, early-onset OCD appears to be a subtype that exhibits distinct clinical features and that is associated with greater familial loading. In the present investigation, South African OCD patients (n=252) were stratified according to age of onset and were clinically assessed. Additionally, selected variants in genes encoding serotonergic and dopaminergic components were investigated in a Caucasian OCD subset (n=180). This subgroup was further stratified to evaluate the role that these candidate genes may play in the genetically homogeneous Afrikaner subset (n=80). Analysis of the clinical data revealed an association between early age of onset and an increased frequency of tics, Tourette's disorder, and trichotillomania (TTM). The genetic studies yielded statistically significant results when the allelic distributions of genetic variants in the dopamine receptor type 4 gene (DRD4) were analysed in the Caucasian OCD cohort. These data support a role for the dopaminergic system, which may be relevant to the development of early-onset OCD.

Adult↗
PubMed2004

Decreased TNF-alpha and NK activity in obsessive-compulsive disorder.

BACKGROUND: Accumulating evidence points towards the involvement of autoimmune mechanisms in the pathophysiology of some subgroups of obsessive-compulsive disorder (OCD). This study was carried out to investigate whether obsessive-compulsive disorder is associated with altered activity of the immune system, and whether these changes are related to particular clinical characteristics. METHODS: Ex vivo production of TNF-alpha, IL-4, IL-6, IL-10, and IFN-gamma in whole blood cultures, and NK-cell activity and peripheral blood NK cell-, monocytes-, T-cell-, and B-cell- percentages were measured in 50 medication-free outpatients with OCD and 25 controls. RESULTS: In OCD patients, we found a significant decrease in production of TNF-alpha (p < 0.0001) and NK-activity (p = 0.002) in comparison with controls. No significant differences were observed in the other immune variables. Patients with first-degree relatives with OCD had significant lower NK-activity than patients who had no relatives with OCD (p = 0.02), and patients with a childhood onset of OCD had significantly lower number of NK-cells than patients with a late onset (p= 0.003). CONCLUSIONS: Changes in TNF-alpha and NK activity suggest a potential role of altered immune function in the pathophysiology of obsessive-compulsive disorder.

Adult↗
PubMed2006

Suicidality in schizophrenic patients with and without obsessive-compulsive disorder.

This report examines the suicidal behaviour in subjects with schizophrenia who have (N=24) and do not have comorbid Obsessive-Compulsive Disorder (OCD) (N=33). The patients with OCD-schizophrenia were more likely to have a previous history of suicidal attempts, and ideations. The number of previous suicidal attempts were significantly higher in patients with OCD-schizophrenia than in patients with non-OCD schizophrenia. The patients with a history of previous suicide attempts were more likely to have a comorbid diagnosis of OCD. Compulsive symptoms were significant predictors of suicide attempt among patients with schizophrenia. Our preliminary findings may suggest that obsessive-compulsive symptoms may account for the emergence of suicidality in patients with OCD-schizophrenia.

Adult↗
PubMed2003

Thought control strategies in obsessive-compulsive disorder: a replication and extension.

Previous research suggests that individuals with OCD use maladaptive strategies to control their unpleasant thoughts (Behav Res Ther (1977) 35, 775). These include worry and self-punishment strategies. In the present study we replicated and extended the previous findings by comparing thought control strategies used by patients with OCD to strategies used by anxious and non-anxious control participants. We also examined changes in thought control strategies for OCD patients who underwent cognitive-behavioral therapy. Compared to controls, OCD patients reported more frequent use of worry and punishment strategies, and less frequent use of distraction. Following successful treatment, OCD patients evidenced increased use of distraction and decreased use of punishment. Findings are discussed in terms of the cognitive model of OCD.

Adult↗
PubMed2003

Is thought-action fusion specific to obsessive-compulsive disorder?: a mediating role of negative affect.

Thought-action fusion (TAF) is a cognitive bias presumed to underlie the development of obsessional problems (i.e. obsessive-compulsive disorder; OCD). Previous studies have found that TAF is related to not only OCD, but also to other anxiety disorders. In the present study we compared levels of TAF in OCD patients and in patients with other anxiety disorders, depression, and healthy controls to examine whether TAF is characteristic of individuals with emotional distress in general, as opposed to anxiety disorders per se. We also examined whether negative affect (i.e. anxiety and depression) mediates the relationship between OCD and TAF. Results indicated that OCD patients were characterized by higher scores on likelihood-self and likelihood-other TAF, but that this difference was predominately due to differences in negative affect. These findings support a model in which negative affect mediates the relationship between OCD and TAF.

Adolescent↗
PubMed2003

Further exploration memory bias in compulsive washers.

The aim of the present study was to replicate Radomsky and Rachman's findings on memory bias in obsessive-compulsive disorder (OCD), using the same procedure but an increased sample size, more specific control groups, and a full analysis of contamination attribution data. Sixteen OCD-washers, 16 OCD-checkers, 16 social phobic patients and 16 non-anxious controls were presented with 50 'clean' or 'dirty' objects. After this incidental encoding phase, participants were asked to freely recall the objects, to rate their anxiety when almost touching each object, and, finally, to attribute each object to one of the two contamination conditions ('clean' or 'dirty'). Verbal episodic memory was also assessed with the California Verbal Learning Test. The results indicate that, contrary to Radomsky and Rachman's findings, OCD-washers did not differ from the other participants in their memory for 'clean' and 'dirty' objects. However, the OCD-washers recalled more accurately the 'dirty' source of contamination than the 'clean' source. This result was specific to the OCD-washers, and suggests a memory bias for contextually threatening information. The differences between our findings and those published by Radomsky and Rachman's are discussed.

Adult↗
PubMed2001

Cerebral metabolic correlates as potential predictors of response to anterior cingulotomy for obsessive compulsive disorder.

BACKGROUND: As interventions for severe, treatment-refractory obsessive compulsive disorder (OCD), neurosurgical procedures are associated with only modest efficacy. The purpose of this study was to identify cerebral metabolic correlates as potential predictors of treatment response to anterior cingulotomy for OCD. METHODS: Clinical data were analyzed in the context of a retrospective design. Subjects were 11 patients who underwent stereotactic anterior cingulotomy for OCD. Symptom severity was measured using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) before and at approximately 6 months postoperative. Preoperative F-18-fluorodeoxyglucose-positron emission tomography (FDG-PET) data were available. Statistical parametric mapping methods were used to identify loci of significant correlation between preoperative regional cerebral metabolism and postoperative reduction in Y-BOCS scores. RESULTS: One locus within right posterior cingulate cortex was identified, where preoperative metabolism was significantly correlated with improvement in OCD symptom severity following cingulotomy. Specifically, higher preoperative rates of metabolism at that locus were associated with better postoperative outcome. CONCLUSIONS: A possible predictor of treatment response was identified for patients with OCD undergoing anterior cingulotomy. Further research, utilizing a prospective design, is indicated to determine the validity and reliability of this finding. If confirmed, an index for noninvasively predicting response to cingulotomy for OCD would be of great value.

Adult↗
PubMed2001

Motor cortex excitability correlates with an anxiety-related personality trait.

BACKGROUND: In an earlier study comparing obsessive-compulsive disorder (OCD) patients to psychiatrically screened normals, we found lowered motor evoked potential (MEP) threshold to transcranial magnetic stimulation (TMS) and decreased intracortical inhibition in OCD. We sought to determine whether this pattern was specific to OCD. METHODS: We measured the threshold and amplitude of MEPs to single and paired (subthreshold-suprathreshold; 3, 4, 10, 15 msec intervals) TMS in 46 healthy volunteers (23 women, 23 men) who were given the NEO-PI-R personality inventory. Nineteen of the men also received cognitive and motor tests. RESULTS: The paired-pulse conditioned/unconditioned MEP amplitude ratios correlated with Neuroticism (N), a stable measure of trait-level anxiety and other negative emotions, in the whole sample (r = 0.48; p = 0.0006), and in the men (r = 0.63; p = 0.0009). There were no other significant correlations. CONCLUSIONS: This relationship reflects a factor that contributes to both personality and cortical regulation. It was not statistically significant in women, probably because of confounding hormonal influences on excitability. Decreased intracortical inhibition may be related more to trait anxiety and depression, which are high in OCD, than to OCD itself. However, the MEP threshold (significantly lowered in OCD) was unrelated to N.

Adolescent↗
PubMed2003

Basal-corticofrontal circuits in schizophrenia and obsessive-compulsive disorder: a controlled, double dissociation study.

BACKGROUND: Several lines of research suggest that prefrontal cortex dysfunctions observed in obsessive compulsive disorder (OCD) and schizophrenia (SKZ) are linked to two partially independent neuroanatomic systems: the ventromedial prefrontal cortex and the dorsolateral prefrontal cortex, with different neuroanatomic connections, including the striatum. The primary aim of this study was to test this hypothesis using a double dissociation study of neuropsychological tasks performance of the dorsolateral prefrontal cortex and ventromedial prefrontal cortex. METHODS: We administered the Wisconsin Card Sorting Test, the Gambling Task, and the four-disk version of the Tower of Hanoi to 110 SKZ and 67 OCD patients and 56 control subjects. RESULTS: A clear double dissociation of Wisconsin Card Sorting Test and Gambling Task performances was found, with SKZ patients performing the Wisconsin Card Sorting test significantly worse than OCD patients and control subjects and OCD patients performing the Gambling Task significantly worse than SKZ and control subjects. Both SKZ and OCD patients performed the Tower of Hanoi significantly worse than control subjects. CONCLUSIONS: Results from our double dissociation study confirm the hypothesis of involvement of different frontal lobe subsystems within basal-corticofrontal circuits function in SKZ and OCD.

Adult↗
PubMed1998

Cognitive deficits in obsessive-compulsive disorder on tests of frontal-striatal function.

BACKGROUND: Although neuropsychological and neuroimaging studies of obsessive-compulsive disorder (OCD) have implicated the frontal cortex and subcortical structures in the pathophysiology of the disorder, few studies have examined cognitive function in patients with OCD on tasks validated in the assessment of frontal lobe and subcortical dysfunction. METHODS: The accuracy and latency of executive and visual memory function was assessed in 23 nondepressed OCD patients and 23 normal healthy controls matched for age, sex, education, and estimated IQ. RESULTS: The patients with OCD performed within the normal range on tasks of short-term memory capacity, delay dependent visual memory, pattern recognition, attentional shifting, and planning ability; however, specific cognitive deficits related to spatial working memory, spatial recognition, and motor initiation and execution were observed in the patient group. These deficits were not correlated with aspects of the patients' intellectual functioning or comorbid psychological symptoms, suggesting that the impairments were related to the specific clinical features of OCD. CONCLUSIONS: Patients with OCD showed specific cognitive deficits on tasks of executive and visual memory function. The pattern of impaired performance in these patients was qualitatively similar to the performance of patients with frontal lobe excisions and subcortical pathology on the same test battery, suggesting that the underlying pathophysiology of the disorder could best be conceptualized as reflecting dysfunction of frontal-striatal systems.

Adult↗
PubMed1998

Intravenous clomipramine challenge in obsessive-compulsive disorder: predicting response to oral therapy at eight weeks.

BACKGROUND: Challenge with intravenous clomipramine (CMI) is serotonin selective and has been reported to transiently exacerbate symptoms in obsessive-compulsive disorder (OCD) patients, and to predict subsequent response to oral CMI therapy. METHODS: We administered CMI (12.5 mg, i.v.) to medication free OCD patients (N = 29) and normal controls (N = 22) to characterize neurohormonal response. A subset of OCD patients (26/29), was then treated with either pulse load i.v. or oral CMI followed by 8 weeks of oral CMI therapy. RESULTS: In response to CMI challenge, OCD patients exhibit blunted cortisol and exaggerated growth hormone response relative to normal controls. OCD patients differ from controls in "sadness" ratings, with control exhibiting increased dysphoria in response to CMI. Growth hormone response to CMI challenge predicts treatment response (> or = 25% decreases YBOCS from baseline) to oral CMI at 8 weeks. CONCLUSIONS: Growth hormone abnormalities associated with OCD in response to CMI challenge differentiates nonresponders after 8 weeks of oral CMI treatment from responders.

Administration, Oral↗
PubMed1998

A.E. Bennett Research Award. Toward a neurodevelopmental model of of obsessive--compulsive disorder.

BACKGROUND: Neurobiological models for obsessive-compulsive disorder (OCD) have consistently implicated ventral prefrontal cortical and striatal circuits in the pathophysiology of this disorder, but typically have not utilized a developmental framework for conceptualizing the illness. METHODS: We describe an integrated series of neurobiologic studies aimed at testing the hypothesis that neurodevelopmental abnormalities of ventral prefrontal-striatal circuits may be involved in and contribute to the etiology and presentation of the illness. RESULTS: Using studies of oculomotor physiology, we have identified a selective deficit in neurobehavioral response suppression in OCD that may be related to failures in the developmental maturation of frontostriatal circuitry. Magnetic resonance imaging studies showed that treatment-naive pediatric OCD patients had significant volumetric abnormalities in ventral prefrontal cortical and striatal regions but no abnormalities in dorsolateral prefrontal cortex. Severity of OCD symptoms but not illness duration was related to ventral prefrontal cortical and striatal volumes. CONCLUSIONS: Critical neurodevelopmental changes in ventral prefrontal-striatal circuitry may be associated with the initial presentation of OCD, and a developmentally mediated network dysplasia may underlie OCD. Such dysplasia in ventral prefrontal cortical circuits could manifest clinically by disrupting brain functions that mediate ongoing purposive behaviors.

Adolescent↗
PubMed1999

Enhanced visual latent inhibition in obsessive-compulsive disorder.

BACKGROUND: Latent inhibition (LI) is the slowed acquisition of a learned response to a conditioned stimulus (CS), that occurs if that CS has previously been experienced in a noncontingent setting. This retarded acquisition is thought to occur because, due to the previous noncontingent experience, an individual must "unlearn the irrelevance" of the CS, before learning its new association to the unconditioned stimulus. A previous report using an auditory paradigm did not detect abnormal LI in obsessive-compulsive disorder (OCD) subjects; this auditory LI task included a difficult acquisition phase, which made it relatively insensitive to detecting abnormally elevated LI (i.e., slowed "unlearning"). METHODS: We assessed LI using a highly sensitive computerized visual LI paradigm in 63 carefully screened control subjects and in 48 patients with OCD. RESULTS: Compared to controls, OCD subjects exhibited significantly more LI; if "preexposed" to a to-be-CS, OCD subjects required significantly more trials to learn a new association to that CS, compared to control subjects. This pattern was particularly evident in unmedicated OCD subjects. CONCLUSIONS: The inflated impact of preexposure on LI response acquisition in OCD subjects may be a quantitative measure of their tendency to remain "stuck in set" in this cognitive task.

Adult↗
PubMed1999

Organizational strategies mediate nonverbal memory impairment in obsessive-compulsive disorder.

BACKGROUND: Previous neuropsychological studies of obsessive-compulsive disorder (OCD) have indicated impaired executive functioning and nonverbal memory. The extent to which impaired executive functioning impacts nonverbal memory has not been established. The current study investigated the mediating effects of organizational strategies used when copying a figure on subsequent nonverbal memory for that figure. METHODS: We examined neuropsychological performance in 20 unmedicated subjects with OCD and 20 matched normal control subjects. Subjects were administered the Rey-Osterrieth Complex Figure Test (RCFT) and neuropsychological tests assessing various aspects of executive function. RESULTS: OCD subjects differed significantly from healthy control subjects in the organizational strategies used to copy the RCFT figure, and they recalled significantly less information on both immediate and delayed testing. Multiple regression analyses indicated that group differences in immediate percent recall were significantly mediated by copy organizational strategies. Further exploratory analyses indicated that organizational problems in OCD may be related to difficulties shifting mental and/or spatial set. CONCLUSIONS: Immediate nonverbal memory problems in OCD subjects were mediated by impaired organizational strategies used during the initial copy of the RCFT figure. Thus, the primary deficit was one affecting executive function, which then had a secondary effect on immediate memory. These findings are consistent with current theories proposing frontal-striatal system dysfunction in OCD.

Adult↗
PubMed2000

Neurobiology of the obsessive-compulsive spectrum disorders.

Advances in obsessive-compulsive disorder (OCD) research have led to increased attention to a range of disorders with possibly overlapping phenomenological and neurobiological features; the so-called OCD spectrum disorders. This article briefly reviews neurobiological data relevant to the construction of an OCD spectrum, including neurochemical, neuroanatomic, genetic, neuroimmunology, and animal studies. OCD and related disorders may be heterogenous conditions, and the neurobiology of many putative OCD spectrum disorders has not been well studied. Nevertheless, a gradual accumulation of neurobiological data has provided a number of exciting, and partially overlapping, approaches to an hypothesized OCD spectrum.

Brain↗
PubMedDate not supplied

The relationship of obsessive-compulsive disorder to putative spectrum disorders: results from an Indian study.

The relationship between obsessive-compulsive disorder (OCD) and putative obsessive-compulsive (OC) spectrum disorders is unclear. This study investigates the prevalence of putative OC spectrum disorders in OCD subjects in a controlled clinical design. The putative OC spectrum disorders studied included somatoform disorders (body dysmorphic disorder [BDD] and hypochondriasis), eating disorders, tic disorders (e.g., Tourette's syndrome [TS]), and impulse control disorders (e.g., trichotillomania). Only those disorders that are commonly noted to be possibly related to OCD are studied. Included in this study were 231 subjects with a diagnosis of OCD according to DSM-IV criteria and 200 controls who were not screened for psychiatric morbidity. The subjects and controls were assessed in detail by extensive clinical and semistructured interviews by expert clinical psychiatrists. The lifetime diagnoses were made by consensus of two psychiatrists. Prevalence of tic disorders, hypochondriasis, BDD, and trichotillomania was significantly greater in OCD subjects compared to controls. However, the prevalence of sexual compulsions, pathological gambling, eating disorders, and depersonalization disorder was not greater in the OCD subjects compared to controls. The findings of this comorbidity study suggest that tic disorders, hypochondriasis, BDD, and trichotillomania are perhaps part of the OC spectrum disorders. There is a need to evaluate evidence from other sources such as epidemiological, neurobiological, and family studies to further our understanding of the concept of OC spectrum disorders.

Adult↗
PubMed2003

Depression and suicidal behavior in adolescent inpatients with obsessive compulsive disorder.

BACKGROUND: To investigate the prevalence and correlations of suicidal behavior in obsessive compulsive disorder (OCD) among adolescent psychiatric inpatients. METHODS: A total of 348 adolescents, representing consecutive admissions to an adolescent inpatient unit, were assessed. Of these, 40 patients had OCD, 118 had schizophrenia, 59 had an affective disorder, 81 had a conduct disorder and 50 had an eating disorder. In addition, 87 normal community controls were assessed. All subjects were assessed for suicidal behavior by the Childhood Suicide Potential Scale (CSPS), for depression by the Beck Depression Inventory, for impulsiveness by the Impulse Control Scale, for anxiety by the State-Trait Anxiety Scale and for aggression by the Yudowsky Overt Aggression Scale. RESULTS: All the psychiatrically ill subjects, including those with OCD, had high levels of depression, anxiety and impulsiveness, which were far higher than those of the controls. The rate of attempted suicide was, however, much lower in the OCD subjects. In addition, there was a significant inverse correlation between suicidal behavior levels on the CSPS and depression in the OCD subjects, while all other subjects showed the expected significant positive correlation between level of suicidal behavior and depression. LIMITATIONS: This study looked at a referred population and generalization to outpatient and community samples cannot be made. Distinguishing between the primary and the comorbid diagnosis is difficult and some findings are based on small sample size and therefore may be vulnerable to type I error. CONCLUSIONS: Although suicidal ideation and depressive symptoms are common in OCD adolescent inpatients, they seem to be protected against suicide attempts. The inverse relationship between suicidal behavior and depression may mean that suicidal behavior is, in some ways, qualitatively different from that seen in other psychiatrically ill adolescents.

Adolescent↗
PubMed2004

Five-minute recordings of heart rate variability in obsessive-compulsive disorder, panic disorder and healthy volunteers.

BACKGROUND: Recent studies have used spectral analysis of heart rate variability (HRV) to study autonomous nervous system (ANS) function in panic disorder (PD). Most studies reported a reduced HRV in resting PD patients, suggesting increased sympathetic and decreased parasympathetic tone. In obsessive-compulsive disorder (OCD) inconsistent findings have been reported on ANS function and to date no studies have been carried out with spectral analysis of HRV. In this HRV study we compared ANS function in patients with PD, OCD and normal controls. METHODS: Standardized HRV measurement was carried out in 24 PD patients, 26 OCD patients and 24 age-matched normal controls. All patients were drug free. As this comparison yielded unexpected results, the PD and normal control samples were enlarged to 53 and 54 subjects, respectively, to verify our first measurement. RESULTS: OCD patients were not characterized by a reduced HRV, as compared to normal controls. This was also found in PD patients, even in the enlarged sample. CONCLUSIONS: HRV analysis in patients with OCD or PD showed that these patients were not characterized by ANS abnormalities, as no evidence was found of diminished HRV in a large sample of resting OCD and PD patients, measured sitting on a hospital bed.

Adult↗