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PubMed2000

On the role of cortical glutamate in obsessive-compulsive disorder and attention-deficit hyperactivity disorder, two phenomenologically antithetical conditions.

OBJECTIVE: The objective of the present study was to compare the phenomenology and pathophysiology of obsessive-compulsive disorder (OCD) and attention-deficit hyperactivity disorder/deficits in attention, motor control and perception (ADHD/DAMP). METHOD: Through detailed studies of the literature on OCD and ADHD/DAMP the phenomenology of these two conditions is compared, and possible underlying pathophysiological mechanisms involving interactions between glutamate, dopamine, serotonin and acetylcholine are discussed, with emphasis on OCD. The present paper also discusses possible mechanisms of action for current pharmacological treatments of OCD and ADHD, as well as possible future treatment strategies for these disorders. RESULTS: OCD and ADHD/DAMP are common neuropsychiatric conditions which in many regards appear to be each other's antipodes with respect to clinical manifestations, associated personality traits and brain biochemistry, notably prefrontal cortical glutamate activity. Future pharmacological treatments of these disorders may involve manipulations with glutamate, dopamine D1, serotonin 2A and nicotine receptors. CONCLUSION: It appears that OCD is a hyperglutamatergic and ADHD a hypoglutamatergic condition, with prefrontal brain regions being especially affected.

Acetylcholine↗
PubMed2000

Symptoms of eating disorders in obsessive-compulsive disorder.

OBJECTIVE: Despite some empirical evidence suggesting an association between primary OCD and eating disorder (ED) within the 'obsessive-compulsive spectrum', the relationship at a symptomatological level has not been investigated. METHOD: First, comparisons of Eating Disorder Inventory (EDI) scores between 61 patients with primary OCD and 288 control subjects were performed. Secondly, the associations between EDI subscores and Hamburg Obsessive-Compulsive Inventory (HZI) dimensions in OCD patients were investigated by multiple regression analyses, controlling for the impact of general psychopathology. RESULTS: The OCD patients showed significantly higher EDI-scores than controls. However, only distinct OCD symptom dimensions were significantly associated with the core symptoms of ED in females. CONCLUSION: Our results point to a differential gender and symptom-specific relationship between OCD and ED, calling into question a simple dimensional conceptualization of the 'obsessive-compulsive spectrum'.

Adult↗
PubMed2003

A follow-up study of juvenile obsessive-compulsive disorder from India.

OBJECTIVE: To study the long-term course and outcome of juvenile obsessive-compulsive disorder (OCD). METHOD: Two to 9-year follow-up of largely self-referred, drug-naïve subjects (n = 58) by employing catch-up longitudinal design. RESULTS: The mean follow-up period was 5 years. Nearly three-fourth of the sample was adequately treated with medications. Only 21% of the subjects had clinical OCD at follow-up and 48% were in true remission (no OCD and not on treatment). Earlier age-at-onset was associated with better course and outcome. CONCLUSION: Juvenile OCD has favorable outcome. Our findings are applicable to psychiatric hospital settings in India and perhaps to the general psychiatric settings in the Western countries. Whether the better outcome in this sample is the result of differing clinical characteristics or because of true cross-cultural variation in the course needs further exploration. It is speculated that early onset OCD could be a subtype of juvenile OCD with better outcome.

Adolescent↗
PubMed2004

Deficits of organizational strategy and visual memory in obsessive-compulsive disorder.

This study was conducted to investigate the deficits of organizational strategy and visual memory in obsessive-compulsive disorder (OCD). Thirty OCD patients and 30 healthy controls aged 20-35 years participated. The Maudsley Obsessive-Compulsive Inventory, Beck Anxiety Inventory, Wechsler Adult Intelligence Scale, and Rey-Osterrieth Complex Figure (ROCF) test were administered to participants. The authors scored ROCF performances using the Boston Qualitative Scoring System. The OCD patients showed poorer planning ability and higher fragmentation than did healthy controls when copying the ROCF, and they showed even poorer performances in the immediate and delayed recall conditions. The authors found that the Organization score in the copy condition mediated the difference between the OCD group and the healthy group in immediate recall. The direct effect of diagnosis (OCD or healthy) on the immediate recall condition of the ROCF was also significant. This study indicates that people with OCD have poor memory function and organizational deficits.

Adult↗
PubMed1998

Evidence for linkage disequilibrium between serotonin transporter protein gene (SLC6A4) and obsessive compulsive disorder.

Obsessive compulsive disorder (OCD) is characterized by recurrent and intrusive thoughts that are distressing (obsessions) and/or repetitive behaviors or mental acts that the person feels driven to perform (compulsions). OCD has a partly genetic basis. For treatment of OCD, potent serotonin reuptake inhibitor (SRI) drugs (clomipramine (Anafranil), fluvoxamine (Luvox), fluoxetine (Prozac), sertraline (Zoloft), and paroxetine (Paxil)), which act on the serotonin transporter protein, are uniquely efficacious. A polymorphism in the promoter region of the gene (SLC6A4) encoding this protein, was recently reported to affect protein expression and to be associated with measures of anxiety and depression and with autism (using a family-controlled transmission disequilibrium test (TDT) design). SLC6A4 therefore has strong a priori support for potentially influencing risk for OCD: the protein it encodes is a medication target; a polymorphism in the gene affects function; and that polymorphism has been shown to be associated with behavioral phenotypes. We used the TDT with a set of 34 European-American family trios, 30 unrelated and four drawn from an extended pedigree, to test for linkage disequilibrium between OCD and alleles at the SLC6A4 promoter polymorphic locus. Of 35 heterozygous parents, 24 transmitted the 'l' SLC6A4 allele and 11 transmitted the 's' allele (chi 2 TDT = 4.83; P < 0.03). Considering only the 13 SRI drug nonresponders, there were 13 heterozygous parents, of whom 10 transmitted the 'l' allele and three the 's' allele (chi 2 TDT = 3.77; P < 0.052). These data provide preliminary support for association and linkage disequilibrium between the SLC6A4 'l' allele and OCD.

Adolescent↗
PubMed2006

Genomewide linkage scan for obsessive-compulsive disorder: evidence for susceptibility loci on chromosomes 3q, 7p, 1q, 15q, and 6q.

Obsessive-compulsive disorder (OCD) is the tenth most disabling medical condition worldwide. Twin and family studies implicate a genetic etiology for this disorder, although specific genes have yet to be identified. Here, we present the first large-scale model-free linkage analysis of both extended and nuclear families using both 'broad' (definite and probable diagnoses) and 'narrow' (definite only) definitions of OCD. We conducted a genome-scan analysis of 219 families collected as part of the OCD Collaborative Genetics Study. Suggestive linkage signals were revealed by multipoint analysis on chromosomes 3q27-28 (P=0.0003), 6q (P=0.003), 7p (P=0.001), 1q (P=0.003), and 15q (P=0.006). Using the 'broad' OCD definition, we observed the strongest evidence for linkage on chromosome 3q27-28. The maximum overall Kong and Cox LODall score (2.67) occurred at D3S1262 and D3S2398, and simulation based P-values for these two signals were 0.0003 and 0.0004, respectively, although for both signals, the simulation-based genome-wide significance levels were 0.055. Covariate-linkage analyses implicated a possible role of gene(s) on chromosome 1 in increasing the risk for an earlier onset form of OCD. We are currently pursuing fine mapping in the five regions giving suggestive signals, with a particular focus on 3q27-28. Given probable etiologic heterogeneity in OCD, mapping gene(s) involved in the disorder may be enhanced by replication studies, large-scale family-based linkage studies, and the application of novel statistical methods.

Chromosomes, Human↗
PubMed1995

Cerebrospinal fluid biogenic amines in obsessive compulsive disorder, Tourette's syndrome, and healthy controls.

To examine the role of noradrenergic, dopaminergic, and serotonergic mechanisms in the pathobiology of obsessive compulsive disorder (OCD) and Tourette's syndrome (TS), concentrations of tyrosine (TYR), norepinephrine (NE), 3-methoxy-4-hydroxyphenylethylene glycol (MHPG), homovanillic acid (HVA), tryptophan (TRP), and 5-hydroxyindoleacetic acid (5-HIAA) were measured in the lumbar cerebrospinal fluid (CSF) of 39 medication-free OCD patients, 33 medication-free TS patients, and 44 healthy volunteers. CSF TYR concentrations were reduced (p < .05) in the OCD patients compared to the healthy subjects. CSF NE in TS patients was 55% higher than in healthy controls (p < .001) and 35% higher than in OCD patients (p < .001). After covarying for height, CSF HVA levels were reduced (p < .05) in the OCD group compared to TS patients but not compared to the normal volunteers. No mean differences in CSF MHPG, TRP, and 5-HIAA were observed in this study across the three groups. The CSF NE data support the hypothesis that noradrenergic mechanisms are involved in the pathobiology of TS. Alterations in the balance of noradrenergic, dopaminergic, and serotonergic systems are likely involved in the pathobiology of OCD.

Adolescent↗
PubMed2002

Obsessive-Compulsive Disorder, 5-HTTLPR polymorphism and treatment response.

Recently, a role for a functional polymorphism within the promoter region of the serotonin transporter gene (5-HTTLPR) in conferring susceptibility to Obsessive Compulsive Disorder (OCD) has been suggested. The aim of this study was to test the hypothesis that allelic variation of the 5-HTTLPR could be associated with OCD susceptibility or influence the drug response in OCD. One hundred and eighty-one OCD patients were recruited; 92 patients underwent a standardized treatment with fluvoxamine. No significant differences in allele/genotype distribution of the 5-HTTLPR were found between 191 controls and OCD. No differences in fluvoxamine response in the three genotypes groups in OCD were found, considering Yale-Brown Obsessive Compulsive Scale (YBOCS) total scores. Nevertheless, a significant time per genotype interaction was found for the YBOCS subtotal compulsion scores. Considering patients without tic disorder co-diagnosis, a significant time per genotype interaction for both YBOCS total scores and compulsion scores was found.

Adult↗
PubMed2003

Features of obsessive-compulsive disorder in patients primarily diagnosed with schizophrenia.

We investigated the prevalence of obsessive-compulsive disorder (OCD) among patients who were primarily diagnosed with schizophrenia. We investigated the differences in the neuropsychiatric features and motor symptoms between patients with schizophrenia who did or did not have OCD. Seventy-one subjects with the DSM-IV diagnosis of schizophrenia were evaluated by the Structured Clinical Interview for DSM-IV Axis I Disorders, the Yale-Brown Obsessive-compulsive Scale and the Positive and Negative Syndrome Scale. To assess their motor symptoms, the Abnormal Involuntary Movements Scale, the Barnes rating scale for drug-induced akathisia and the Simpson and Angus extrapyramidal symptoms (EPS) rating scale were used. The 13 subjects with OCD (18.3%) had significantly more severe motor symptoms than the non-OCD subjects. Patients with schizophrenia who exhibit moderate to severe motor symptoms as side-effects of neuroleptics, should be examined for OCD comorbidity. Patients who are found to have OCD comorbidity must be treated with carefully chosen medications, including serotonin re-uptake inhibitors.

Adult↗
PubMedDate not supplied

Bulimia nervosa with and without obsessive-compulsive syndromes.

The present study was performed in a group of bulimic (BN) females (1) to assess prevalence rates of comorbid obsessive-compulsive phenomena; (2) to investigate whether BN patients display a characteristic cluster of obsessive-compulsive symptoms; and (3) to determine whether obsessive-compulsive symptoms influence the clinical picture of BN. Thirty-eight DSM-IV BN females were interviewed by means of the Structured Clinical Interview for DSM-III-R (SCID) to assess the prevalence rate of obsessive compulsive disorder (OCD); the Yale-Brown Obsessive-Compulsive Symptom Scale (Y-BOCS) Symptom Check-List was also used to evaluate the presence of obsessive-compulsive symptoms. The phenomenology of BN females with obsessive-compulsive syndromes (OCS) as detected by the Y-BOCS was compared to that shown by a "control" group of nonbulimic OCD females. Finally, the eating-related psychopathology of BN women with and without OCS was compared. The current prevalence rates of OCD and of subthreshold obsessive-compulsive syndrome (sOCS) in our sample were 10.5% and 15.8%, respectively. Thus, a total of 26.3% of BN females had a current OCS that comprised both clinical disorders and subthreshold syndromes. No differences were detected between obsessive-compulsive symptoms of these females and those of the control group of nonbulimic OCD females. BN females with OCS had higher ratings on the Eating Disorder Inventory (EDI) total score and on the "drive for thinness" and the "bulimia" items of the scale, as compared to BN females without OCS. In conclusion, it appears that a considerable proportion of BN females display OCS, which sometimes are not severe enough to fulfill diagnostic criteria for OCD. Moreover, in these patients, obsessive-compulsive symptoms are undistinguishable from those of OCD females, and exert a negative influence on the clinical picture of the bulimic disorder.

Adult↗
PubMed2001

Osteochondritis dissecans of the lateral femoral condyle following total resection of the discoid lateral meniscus.

PURPOSE: The purpose of this study was to describe the clinical presentation of 6 athletically active children with symptomatic osteochondritis dissecans (OCD) of the lateral femoral condyle following total resection for a torn discoid lateral meniscus and to discuss its cause. TYPE OF STUDY: Case series. METHODS: Six patients in whom OCD affecting the lateral femoral condyle developed after total resection of the discoid lateral meniscus participated in a detailed clinical, radiologic, and arthroscopic review. The average age at the time of meniscectomy was 9 years (range, 6 to 12 years). At a mean of 50 months (range, 36 to 65 months) after surgery they developed recurrent pain in the treated knee; all had radiologic abnormalities at the lateral femoral condyle consistent with OCD. Before the recurrence of pain, all patients had been continuously engaged in sports activity. Radiologic and arthroscopic findings of the OCD lesions were assessed. Clinical outcomes of surgical treatment for OCD were also documented. RESULTS: The radiographic evaluation showed all lesions to be in the central portion of the lateral femoral condyle on the anteroposterior views and posteriorly next to a line extending distally from the posterior femoral cortex on the lateral views. Arthroscopic evaluation revealed softening in 2 knees, a separated fragment in 2 knees, and a completely loose fragment in 2 knees. All lesions were treated surgically, including 2 drillings of the lesion, 2 fixations of separated fragment, and 2 excisions of loose bodies with drilling. At an average follow-up period of 51 months (range, 22 to 77 months), all patients but 1 were asymptomatic. CONCLUSIONS: Repeated impaction in sports activities on the immature osteochondral structures under altered mechanical force transmission after total resection of the discoid meniscus might be a predisposing factor in the development of OCD in the lateral femoral condyle.

Adolescent↗
PubMed2001

Brain-behavior relationships in obsessive-compulsive disorder.

Advances in neuroimaging have led to a greater understanding of brain-behavior relationships in obsessive-compulsive disorder (OCD). This article provides an updated review and analysis of the structural and functional neuroimaging studies in OCD published to date and discusses how evidence from various types of neuroimaging studies has been synthesized to generate and test hypotheses regarding these relationships. We also review the basic science literature on the functional neuroanatomy of cortico-basal ganglia-thalamo-cortical circuits and integrate this information with neuroimaging data in OCD, to present a theoretical model of brain mediation of OCD symptoms and response to treatment. Taken together, neuroimaging studies indicate that OCD symptoms are mediated by hyperactivity in orbitofrontal-subcortical circuits, which may be attributable to an imbalance of tone between direct and indirect striato-pallidal pathways. Serotonergic drugs may ameliorate OCD symptoms by changing the relative balance of tone through the indirect versus direct orbitofrontal-subcortical pathways, thereby decreasing activity in the overall circuit that exists in the symptomatic state.

Brain↗
PubMed1996

Brain Mediation of Obsessive-Compulsive Disorder Symptoms: Evidence From Functional Brain Imaging Studies in the Human and Nonhuman Primate.

Obsessive-compulsive disorder (OCD) has a long history of speculations concerning its cause. This article reviews human functional neuroimaging studies of OCD, then presents data from a study in the nonhuman primate that concerns the localization of brain systems that may mediate the expression of OCD symptoms. We use these lines of evidence to argue that increased "neural tone" through a section of the behaviorally disinhibiting "direct" basal ganglia pathway, relative to tone in the behaviorally inhibiting or moderating "indirect" basal ganglia system, may mediate the expression of OCD symptoms. The limbic orbital prefrontal cortex, the involvement of which is highly implicated in OCD, may have a greater influence on neural tone in the direct pathway than in the indirect, whereas more dorsal neocortical prefrontal regions may have the opposite effects on these two basal ganglia subsystems. Effective OCD treatments may obtain their results by preferentially decreasing neural tone through the direct relative to the indirect basal ganglia system.

Journal Article↗
PubMed1996

Issues Involved in Recognizing Obsessive-Compulsive Disorder in Developmentally Disable Clients.

Certain unusual behaviors in people with developmental disabilities might be unrecognized obsessive-compulsive disorder (OCD). Compulsions, in persons unable to think abstractly or count, can appear differently from compulsions in persons able to comprehend concepts like contamination and counting sequences. The content of obsessive speech also varies depending on the comprehension and vocabulary of the person with OCD. People not showing classic symptoms of OCD have been at risk for this disorder not being recognized. Researchers report that certain medications are ineffective or worsen OCD, and that developmentally disabled people with undiagnosed OCD are at risk for being put on such medications. This article provides information to facilitate the recognition of OCD in developmentally disabled clients.

Journal Article↗
PubMed2006

[Subjective quality of life of patients with obsessive-compulsive disorder compared to the general population].

BACKGROUND: Patients with obsessive-compulsive disorder (OCD) not only suffer from obsessive-compulsive symptoms, but also the disorder is associated with impaired social functioning, which impact their everyday life negatively. OBJECTIVE: Subjective quality of life (QoL) in patients with OCD was examined and compared to the general German population. METHODS: 75 patients with OCD (ICD-10 F42.0-F42.2) were recruited from the outpatient clinic for anxiety disorders at the Department of Psychiatry of the University of Leipzig. Patients showing psychiatric co-morbidity were excluded. By means of the WHOQOL-BREF, QoL was assessed in patients with OCD and in a sample of the general population of Saxony/Germany. RESULTS: Compared with the general population, QoL in patients with obsessive-compulsive disorders was lower in all domains of the WHOQOL-BREF. CONCLUSION: OCD has a substantial adverse effect on patients' subjective QoL. Therefore, it will be necessary to include interventions in the treatment of OCD aimed at improving residual deficits in psychosocial functioning and QoL.

Adolescent↗
PubMed1991

[Psychobiology of compulsive disease].

The predominant psychobiological hypotheses regarding the pathophysiology of obsessive-compulsive disorder (OCD) are that a selective basal ganglia dysfunction and a dysregulation of one or several central serotonin (5-HT) subsystem are related to at least some aspects of the syndrome. Recent neuroanatomical, -pharmacological, and -ethological studies indicate a complex perceptual and cognitive role for the basal ganglia, particularly the striatum and the pallidum, in addition to the well-established motor functions. Obsessive-compulsive symptoms in syndromes with extrapyramidal-motor dysfunction, such as Gilles de la Tourette syndrome or Chorea minor (Sydenham), response to specific pharmacotherapy, behavioural therapy, and psychosurgery, as well as findings derived from brain imaging studies including positron emission tomography (PET) support the view of a frontal cortex/basal ganglia dysfunction in OCD. In addition, growing evidence suggests that potent inhibitors of 5-HT reuptake and other 5-HT subsystem-selective agents, such as the azapirones with partial agonist properties at the 5-HT1A receptor, are effective in OCD not only has improved the therapeutic perspective but may also reveal clues to the aetiopathogenesis of OCD. Much of this evidence has resulted from the discovery of multiple receptors and signal transduction pathways for 5-HT and from experiments relating the action of 5-HT receptor-selective agents to discrete effects in different subsystems. Among these 5-HT subsystems the 5-HT1D and 5-HT1A receptor-effector system complex appears to play a central role in the pathophysiology of OCD symptoms and the mechanism of action of antiobsessional drugs. Recent psychoneurobiological findings are reviewed briefly and evaluated in the context of the 5-HT and basal ganglia hypothesis of OCD.

Basal Ganglia↗
PubMed1990

Obsessive-compulsive disorder: suffering in silence.

Obsessions and compulsions vary in frequency and intensity. Many individuals have habits that cause minimal or no disruption of their lives. OCD, however, causes significant distress and interference with daily life. The problem may go unnoticed by anyone except the involved individual, or it may involve family, friends, and acquaintances. The disorder can be disabling, adversely affecting a student personally, socially, and occupationally. Those who are significantly affected by OC symptoms are encouraged to seek treatment. Behavior therapy and medications are extremely beneficial in helping to relieve symptoms of OCD. Clomipramine and fluoxetine (Prozac) are new drugs available in the US that appear to be effective for OCD symptoms. Several other anti-OCD medications may be available in the US within the next few years. It is important that students and others on campus be made aware that OCD is more common than previously recognized, that more persons with OCD are seeking help, and that effective treatment is available. This "secretive," often disabling disorder is more open now, and it is to be hoped that more individuals will take advantage of current, effective evaluation and treatment modalities.

Adolescent↗
PubMed2001

Autistic traits in obsessive-compulsive disorder.

In contrast to other non-psychotic psychiatric populations, subjects with obsessive-compulsive disorder (OCD) are more prone to have personality disorder from cluster A (the odd and eccentric cluster). The present study aims at further investigating the relationship between these and other personality traits in OCD subjects and their relation to high functioning autism (HFA) and Asperger disorder. Sixty-four subjects with OCD were included. Personality traits were assessed with the Karolinska Scales of Personality (KSP), and personality disorders with DSM-adapted questionnaires. In addition, autistic traits were assessed in 29 videotaped subjects, by 3 independent raters. Twenty percent of the subjects with OCD were identified as also having autistic traits. These subjects scored higher on KSP scales measuring muscular tension, psychasthenia, and inhibition of aggression and lower on socialization as compared with OCD subjects without autistic traits. Additionally, subjects with autistic traits fulfilled criteria for anxious personality disorders and paranoid personality disorders significantly more often than subjects without autistic traits. We propose that OCD is often related to HFA and Asperger disorder. Self-report questionnaires may be useful in establishing the diagnosis. However, those with the most obvious autistic features seem to be less able to identify these traits in themselves.

Adolescent↗