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This study sought to examine quality of life (QoL) in clinic-referred children and adolescents (n = 59, M age = 11.4+/-2.6 years) with a chronic tic disorder. The QoL scores for tic patients were lower than for healthy controls but higher than for the psychiatric sample on the majority of domains. Children's self-reported QoL scores and a measure of tic severity were moderately and inversely correlated. Parent reports of their child's QoL were weakly related to tic severity. Correlations between parent and child ratings of QoL for children ages 8 to 11 years were generally higher than those for youth ages 12 to 17 years. Finally, externalizing behavior moderated the relations between tic severity and parent-rated QoL, such that tic severity was significantly associated with parent-rated QoL for children with below average externalizing symptoms but not for children 3with above average externalizing symptoms.

Currently, there are limited published data evaluating the effects of tics on serotonin reuptake inhibitor (SRI) monotherapy responses in treating obsessive-compulsive disorder (OCD). One retrospective case-controlled analysis of OCD patients treated with SRI monotherapy showed lesser improvement in OCD symptoms in patients with tics than those without. However, more recently there were preliminary reports of OCD subjects treated with SRI monotherapy which did not demonstrate poorer response in subjects with tics or Tourette's Syndrome (TS). The specific aim of this study was to investigate whether the presence of comorbid chronic tics affected "clinically meaningful improvement" [McDougle, C.J., Goodman, W.K., Leckman, J.F., Barr, L.C., Heninger, G.R., Price, L.H., 1993. The efficacy of fluvoxamine in obsessive-compulsive disorder: effects of comorbid chronic tic disorder. Journal of Clinical Psychopharmacology 13, 354-358] of OCD in an 8-week open-label trial of fluoxetine monotherapy. Seventy-four adult subjects (13 patients with comorbid chronic tics and 61 patients without tics) with a primary DSM-IV OCD diagnosis were treated with up to 40mg fluoxetine for 8 weeks and had at least one post-baseline evaluation. The results indicate that there was a significant response by time in both fluoxetine-with-tic subjects and fluoxetine-without-tic subjects. Additionally, there were 3 (23.0%) OCD subjects with tics who had clinically meaningful improvement versus 16 (26.2%) OCD subjects without tics that demonstrated similar levels of improvement. These findings indicate that OCD patients with or without chronic tic disorders did not have a differential response to an 8-week open-label trial of fluoxetine. Limitations include the relatively low number of tic subjects and the open-label nature of the study. Additional data are needed on how comorbid tics may affect SRI treatment response in OCD.

Objective: To examine the relative efficacy of intensive versus weekly cognitive-behavioral therapy (CBT) for children and adolescents with obsessive-compulsive disorder (OCD)., Method: Forty children and adolescents with OCD (range 7-17 years) were randomized to receive 14 sessions of weekly or intensive (daily psychotherapy sessions) family-based CBT. Assessments were conducted at three time points: pretreatment, posttreatment, and 3-month follow-up. Raters were initially blind to randomization. Primary outcomes included scores on the Children's Yale-Brown Obsessive-Compulsive Scale, remission status, and ratings on the Clinical Global Impression-Severity and Clinical Global Improvement scales. Secondary outcomes included the Child Obsessive Compulsive Impact Scale-Parent Rated, Children's Depression Inventory, Multidimensional Anxiety Scale for Children, and Family Accommodation Scale. Adjunctive pharmacotherapy was not an exclusion criterion., Results: Intensive CBT was as effective as weekly treatment with some advantages present immediately after treatment. No group differences were found at follow-up, with gains being largely maintained over time. Although no group x time interaction was found for the Children's Yale-Brown Obsessive-Compulsive Scale (F(1,38) = 2.2, p = .15), the intensive group was rated on the Clinical Global Impression-Severity as less ill relative to the weekly group (F(1,38) = 9.4, p < .005). At posttreatment, 75% (15/20) of youths in the intensive group and 50% (10/20) in the weekly group met remission status criteria. Ninety percent (18/20) of youths in the intensive group and 65% (13/20) in the weekly group were considered treatment responders on the Clinical Global Improvement (chi1(2) = 3.6, p = .06)., Conclusions: Both intensive and weekly CBT are efficacious treatments for pediatric OCD. Intensive treatment may have slight immediate advantages over weekly CBT, although both modalities have similar outcomes at 3-month follow-up.

Objectives: This article reviews evidence that led the Food and Drug Administration to issue a "black box" warning about the risk of "suicidality" (suicidal thoughts and behavior) in children and adolescents during treatment with antidepressants., Results: Re-analysis of data from randomized clinical trials of antidepressants in the pediatric population revealed a significantly greater overall (all drugs across all indications) risk ratio for drug 1.95 (95% Cl, 1.28-2.98) compared to placebo in this sample of approximately 4,000 subjects., Discussion: The essential message of the "black box" is to remind prescribers and consumers about the importance of monitoring closely for adverse behavioral changes during the initiation of (or changes in) antidepressant therapy. Possible mechanisms that might account for this phenomenon, particularly the so-called activation syndrome, are discussed., Conclusion: Empirical studies are needed to identify the precursors of suicidality and to predict which individuals are most susceptible to adverse behavioral side effects of antidepressants.

Background: Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus (PANDAS) research is based on the hypothesis that infections trigger changes in behavior and movement in children., Methods: We enrolled 693 children (ages 3 to 12 years) into a systematic, longitudinal study. Data were collected monthly for 8 months (October-May) to determine point prevalence of Group A Streptococcal (GAS) infections, tics, behavior, and choreiform movements. Simultaneous throat cultures were obtained, and relational analyses were made between GAS and movement/observation ratings., Results: Combined behavior/GAS associations (concurrent with or 3 subsequent months to GAS) revealed a strong relationship, relative risk (RR) of 1.71 (p < .0001). Detailed analysis revealed that balance/swaying and non-tic grimacing were responsible for a significant proportion of this association (RR = 2.92, p < .0001). A strong seasonal pattern was found, with fall being more significant for GAS infections and observation ratings (p < .0001) compared with winter/spring. Children with repeated streptococcus (n = 64) showed higher rates of behavior and distal choreiform observations (p = .005)., Conclusions: Motor/behavior changes were noted to occur in relationship to positive GAS culture with support that repeated GAS increases risk.

We report on the factor structure of the Yale Global Tic Severity Scale. Participants were 76 children and adolescents diagnosed with tic disorders. Overall, the model proposed by Leckman et al. [Leckman, J.F., Riddle, M.A., Hardin, M.T., Ort, S.I., Swartz, K.L., Stevenson, J., Cohen, D.J., 1989. The Yale Global Tic Severity Scale: initial testing of a clinician-rated scale of tic severity. Journal of the American Academy of Child and Adolescent Psychiatry 28, 566-573.] represented an adequate fit. The internal consistency of the factors was acceptable and the convergent and divergent validity was supported vis-à-vis correlations with parent ratings of Tourette's Disorder symptoms. These findings support the use of the original scoring structure in assessing pediatric tic severity.

Few data have been reported on the efficacy of cognitive-behavioral therapy (CBT) for youth with obsessive-compulsive disorder (OCD) who have not responded to prior treatment with medication. Given this, we report an open trial of CBT for children who have remained symptomatic following medication trials. Five children with OCD who had an inadequate response to psychotropic medications (e.g., limited response and/or unable to be titrated to a complete dose due to side effects) received treatment in a 3-week intensive CBT program. Assessments were conducted at baseline and after treatment. All participants were classified as treatment responders (much improved or very much improved) and the severity of clinician-rated OCD symptoms and impairment significantly decreased after the intervention. Although a number of limitations of this preliminary report exist, this study provides preliminary support for the utility of an intensive intervention for youth with OCD who have had an inadequate response and/or adverse side effects., ((c) 2006 Wiley-Liss, Inc.)

Deep brain stimulation (DBS) of the anterior limb of the internal capsule has been shown to be beneficial in the short term for obsessive-compulsive disorder (OCD) patients who exhaust conventional therapies. Nuttin et al, who published the first DBS for OCD series, found promising results using a capsule target immediately rostral to the anterior commissure extending into adjacent ventral capsule/ventral striatum (VC/VS). Published long-term outcome data are limited to four patients. In this collaborative study, 10 adult OCD patients meeting stringent criteria for severity and treatment resistance had quadripolar stimulating leads implanted bilaterally in the VC/VS. DBS was activated openly 3 weeks later. Eight patients have been followed for at least 36 months. Group Yale-Brown Obsessive Compulsive Scale (YBOCS) scores decreased from 34.6+/-0.6 (mean+/-SEM) at baseline (severe) to 22.3+/-2.1 (moderate) at 36 months (p < 0.001). Four of eight patients had a > or =35% decrease in YBOCS severity at 36 months; in two patients, scores declined between 25 and 35%. Global Assessment of Functioning scores improved from 36.6+/-1.5 at baseline to 53.8+/-2.5 at 36 months (p < 0.001). Depression and anxiety also improved, as did self-care, independent living, and work, school, and social functioning. Surgical adverse effects included an asymptomatic hemorrhage, a single seizure, and a superficial infection. Psychiatric adverse effects included transient hypomanic symptoms, and worsened depression and OCD when DBS was interrupted by stimulator battery depletion. This open study found promising long-term effects of DBS in highly treatment-resistant OCD.

Objective: To provide preliminary estimates of the effectiveness of cognitive-behavioral therapy (CBT) in treating pediatric obsessive-compulsive disorder (OCD) of the pediatric autoimmune neuropsychiatric disorders associated with streptococcus (PANDAS) subtype., Method: Seven children with OCD of the PANDAS subtype (range 9-13 years) were treated in a 3-week intensive CBT program conducted at a university clinic. Six of seven children were taking selective serotonin reuptake inhibitor medication(s) upon presentation. Assessments were conducted at four time points: baseline, pretreatment approximately 4 weeks later, posttreatment, and 3-month follow-up. Raters were blind to the nature of the study treatment., Results: Six of seven participants were classified as treatment responders (much or very much improved) at posttreatment, and three of six remained responders at follow-up. Clinician severity ratings, as measured by the Children's Yale-Brown Obsessive-Compulsive Scale and Anxiety Disorder Interview Schedule for DSM-IV Child Interview Schedule-Parent version, decreased significantly following intervention, with effect sizes of 3.38 and 2.29, respectively. Self-reported general anxiety and depression symptoms were not significantly reduced., Conclusions: This study provides preliminary support for CBT in treating the PANDAS subtype of pediatric OCD. This approach is also considered a safe and minimally invasive treatment approach.

This study examined the frequency of peer victimization and psychological symptom correlates among youth with obsessive-compulsive disorder (OCD). The Schwartz Peer Victimization Scale, Children's Depression Inventory, and Asher Loneliness Scale were administered to 52 children and adolescents diagnosed with OCD. The child's parent or guardian completed the Child Behavior Checklist, and a trained clinician administered the Children's Yale-Brown Obsessive-Compulsive Scale (CY- BOCS). Fifty-two healthy controls and 52 children with Type 1 diabetes (T1D) who were administered the Schwartz Peer Victimization Scale as part of another study were included for comparison purposes. Greater rates of peer victimization were reported in youth with OCD relative to healthy controls and children with Type 1 diabetes (T1D). Peer victimization in the OCD sample was positively related to loneliness, child-reported depression, parent-reported internalizing and externalizing symptoms, and clinician-rated OCD severity. Peer victimization fully mediated the relation between OCD severity and both depression and parent reports of child externalizing behaviors and partially mediated the relation between OCD severity and loneliness. Recognition of the magnitude of the problem and contribution problematic peer relations may play in comorbid psychological conditions is important for clinicians who see children with OCD.

Several lines of evidence suggest a meaningful association between obsessive-compulsive disorder and Tourette syndrome, including comorbidity, phenomenologic overlap, evidence from family and genetic studies, and the possible role of basal ganglia circuitry in both conditions. Obsessive-compulsive behaviors occur frequently in patients who have Tourette syndrome and tend to have a later onset than tics. Despite commonalities, the approaches to treating tics and obsessive-compulsive symptoms are actually quite distinct. A specialized form of cognitive behavior therapy and pharmacotherapy with a potent serotonin reuptake inhibitor are the two established first-line therapies for obsessive-compulsive disorder. An adequate trial of a serotonin reuptake inhibitor is 10 to 12 weeks in duration at doses near the upper end of the recommended range for age and weight. Cases of obsessive-compulsive disorder that do not sufficiently improve with serotonin reuptake inhibitors might benefit from adjunctive low-dose antipsychotic (eg, risperidone) medication whether or not tics are present. Warnings about an increased risk of suicidality among children and adolescents taking antidepressants for pediatric depression extend to those taking the medications for obsessive-compulsive disorder, but the risk-to-benefit ratio is more favorable in this latter population because several serotonin reuptake inhibitors have been shown to be efficacious in obsessive-compulsive disorder.

The introduction of deep brain stimulation (DBS) as a treatment for medication-refractory essential tremor in the late 1980s revealed, for the first time, that "chronically" implanted brain hardware had the potential to modulate neurologic function with surprisingly low morbidity. Over time, the therapeutic promise of DBS has become evident in Parkinson's disease and dystonia. In some experienced centers, complex tremor disorders, such as posttraumatic Holmes tremor and the tremor of multiple sclerosis, are being increasingly targeted. More recently, other indications, including obsessive-compulsive disorder, Tourette's syndrome, major depression, and chronic pain, have been proposed. As the field has expanded, our knowledge about potential cognitive side effects of DBS has also expanded. This article reviews the current knowledge regarding the impact of stimulation of the subthalamic nucleus, globus pallidus internus, and ventralis intermedius nucleus of the thalamus on symptoms in essential tremor, Parkinson's disease, and dystonia. Also discussed are the emerging targets, what is known about the cognitive sequelae of DBS, and what has been learned about the complications and therapeutic failures.

Childhood OCD often develops into a chronic illness that lasts decades. Proof that some type of immunotherapy (such as antibiotic prophylaxis) could significantly reduce recurrence or exacerbation of symptoms of OC or tics would suggest a supportive role for immune triggers in the onset or worsening of these conditions and provide additional tools for improving outcome. The validity of PANDAS will continue to be questioned, however,because demonstrating a clear causation will be difficult on a background ofa common childhood illness. Along with the previously mentioned immuno-therapy study, validation of the PANDAS phenotype (broadly interpreted)would be advanced from new and continued research in the following areas: (1) prospective studies to identify infectious triggers in the onset and exacerbations of OCD spectrum disorders, (2) biological measures for immune and genetic susceptibility, and (3) large scale epidemiological studies demonstrating the relationship between infection and OCD spectrum disorders. The assimilation of these study results should allow for elucidation of the immune system's role in the onset and maintenance of OCD.

Human and animal research has shown that the ventral striatum, including the nucleus accumbens, may play a critical role in mediating positive emotions. Recently we described a subject with obsessive-compulsive disorder who intra-operatively exhibited the acute onset of an asymmetric smile and acute positive emotional change with contralateral deep brain stimulation (DBS) in either the right or left nucleus accumbens and anterior limb of the internal capsule region. The purpose of the present study was to examine the stability of the stimulation-induced smile(s) over a 12-month period. Custom computer software objectively quantified left and right facial movement during DBS. Although stimulation-induced smiles were elicited at one and two months post-surgery, they were no longer present from 3-12 months following chronic high frequency DBS. The smiles could not be elicited even with long washout periods. These findings imply potential long-term habituation and changes in the neural chemistry (possibly neuroplasticity) induced by chronic DBS.

Recent evidence from human research has indicated that discrete regions of the brain control different basic emotions. Whether the recognition and formulation of emotions truly stem from compartmentalized systems or arise from a multidimensional framework has yet to be elucidated, however. Disgust is a basic emotion that has been hypothesized to constitute an evolutionary function of contamination and disease avoidance. Disgust involves the appraisal of objects and events for their potential role in contamination, and OCD conceivably involves a dysfunction of this appraisal process. Disgust sensitivity has been shown to be positively correlated with OCD and to significantly predict contamination fear. Likewise, functional imaging studies of OCD patients with contamination concerns demonstrate activation of the same neural regions with disgust-inducing pictures as symptom relevant stimuli. Therefore, the neurocircuits involved in disgust processing may be relevant to OCD and, in particular, the contamination subtype. This review focuses on describing what is known to date concerning the neurocircuitry of disgust, and its relevance to the apparent neurocircuitry of OCD.

Pediatric obsessive-compulsive disorder (OCD) is a chronic neuropsychiatric condition associated with broad impairments in functioning. This paper outlines current etiological theories of OCD, providing a review of neuroanatomical, neurochemical, neuroimmunological, and cognitive-behavioral explanations. Subsequently, first-line treatment modalities are discussed (serotonin reuptake inhibitors [SRIs] and cognitive-behavioral therapy [CBT] with exposure and response prevention [E/RP]) in the context of recent pharmacological, CBT, and combined trials.

Despite wide use, relatively little is known about sociodemographic and clinical characteristics that predict early fluoxetine response. What research has been conducted has produced inconsistent findings, which may be due to the statistical procedures used, and no studies to date have examined predictors of early fluoxetine treatment response. Sixty adults with obsessive-compulsive disorder (OCD) completed an open-label fluoxetine trial for 8 weeks (up to 40 mg) after a 1-week, single-blind, placebo run-in before baseline assessment. The baseline and posttreatment assessment battery included the Yale-Brown Obsessive Compulsive Scale, the Hamilton Rating Scale for Depression, and the Yale Global Tic Severity Scale. Patient characteristics included illness duration, age, age of onset, gender, and pharmacological treatment history. Independent t-tests and multiple logistic regression analysis showed that longer illness duration, older age, and greater symptom severity were associated with nonresponse. Our findings highlight the impact of functional psychiatric impairment on determining those who may respond to treatment. Furthermore, findings suggest early predictors of patients with certain characteristics who may ultimately need adjunctive care to facilitate response.

This study examined the psychometric properties of the Obsessive-Compulsive Scale (OCS) of the Child Behavior Checklist (CBCL). Participants included 48 youth with obsessive-compulsive disorder (OCD), 41 with a non-OCD internalizing disorder, and 101 with an externalizing disorder. Confirmatory factor analysis of the 8-item OCS did not result in an adequate fit. Exploratory factor analysis identified a 1-factor model consisting of 6 items. Adequate internal consistency for the revised OCS (OCS-R) was obtained, and convergent validity was supported by moderate relationships with other OCD indices. The OCS-R had stronger associations with measures of OCD symptoms than with measures of depression and externalizing behaviors. Youth with OCD had significantly higher OCS-R scores than those with internalizing and externalizing disorders. Suggestions for cutoff scores are provided using results from ROC analyses. Overall, these findings suggest that the OCS-R is a reliable and valid instrument for the assessment of pediatric OCD.

The children's Yale-Brown obsessive-compulsive scale (CY-BOCS) is a commonly used, psychometrically sound clinician-rated instrument of pediatric obsessive-compulsive disorder (OCD) severity. Given the relatively direct rating format and potential benefits of alternative versions that could be easily administered to patients and parents, we developed and examined the psychometric properties of child- and parent-report formats of the CY-BOCS severity items. A total of 53 children and adolescents (8-17 years old) with OCD and their parents was administered the CY-BOCS, children's Yale-Brown obsessive-compulsive scale-child report (CY-BOCS-CR), children's Yale-Brown obsessive-compulsive scale-parent report (CY-BOCS-PR), and other measures of obsessive-compulsive symptoms, internalizing, and externalizing symptoms. In general, reliability and convergent and divergent validity of the CY-BOCS-CR/PR were satisfactory. Psychometric properties for the CY-BOCS-CR in those children and adolescents with externalizing behavior problems were lower relative to those without externalizing problems. Exploratory factor analyses identified a two-factor structure in both measures comprised of disturbance and severity factors. This study provides preliminary support for the use of child- and parent-report versions of the CY-BOCS.

Obsessive-compulsive disorder (OCD) affects approximately 2-4% of the adult population. Despite the practical and emotional demands of having a family member with OCD, few systematic attempts have been made to assess the coping strategies used by relatives of individuals with such diagnoses. In this study we examined the relationships between hope, coping strategies, and depressive symptoms in a heterogeneous sample of 67 spouses/primary caregivers of individuals with a history of OCD. In support of our hypotheses, hope was negatively related to depressive symptoms, symptom severity, and denial disengagement coping strategies, and positively related to active reframing and social support coping strategies. Active, Reframing, Social Support, and Religiosity were negatively related to depressive symptoms. Denial/Disengagement was positively associated with depressive symptoms. Coping mediated the relationship between hope and depressive symptoms. Given the importance of family members in treatment, clinical implications of these findings are discussed.

Obsessive-compulsive disorder (OCD) is a relatively common disorder among children and adolescents, and is associated with increased risk for concurrent and future distress and impairment. Many youth who suffer from OCD go undiagnosed or misdiagnosed, and do not attain appropriate treatment in a timely manner. As a result, researchers have focused greater attention to the assessment of pediatric OCD. This paper provides an overview of recent advances in this area, including an introduction to several new assessment instruments. Descriptions of new and commonly used instruments and their clinical/research utility are described. Psychometric properties are also reported. Finally, a critical review is offered of major trends in the assessment of pediatric OCD (e.g., diagnostic interviews, self-report and parent-report measures, and clinician-administered inventories).

To investigate the reliability and validity of the Yale Global Tic Severity Scale (YGTSS), 28 youth aged 6 to 17 years with Tourette's syndrome (TS) participated in the study. Data included clinician reports of tics and obsessive-compulsive disorder (OCD) severity, parent reports of tics, internalizing and externalizing problems, and child reports of depression and anxiety. All children participated in a 2nd YGTSS administration by the same rater 48 days later. Good internal consistency and stability were found for the YGTSS scores. YGTSS scores demonstrated strong correlations with parent-rated tic severity (r = .58-.68). YGTSS scores were not significantly related to measures of clinician ratings of OCD severity (r = .01-.15), parent ratings of externalizing and internalizing behavior (r = -.07-.20), and child ratings of depression (r = .02-.26) and anxiety (r = -.06 -.28). Findings suggest that the YGTSS is a reliable and valid instrument for the assessment of pediatric TS.

Background: Escitalopram 10 mg/day is an effective and well-tolerated antidepressant. Three randomized controlled trials recently evaluated the safety and efficacy of escitalopram in the treatment of generalized anxiety disorder (GAD)., Methods: The trial designs were virtually identical, allowing data to be pooled across studies. Male and female outpatients, ages 18-80 years, with DSM-IV-defined GAD were randomized to double-blind treatment with escitalopram or placebo for 8 weeks. Escitalopram dose was fixed at 10 mg/day for the first 4 weeks, after which increases to 20 mg/day were permitted. The primary efficacy variable was the mean change from baseline in total Hamilton Anxiety Scale (HAMA) score., Results: Approximately 850 patients were randomized to double-blind treatment. In each individual study, escitalopram was significantly superior to placebo (p<0.05) as measured by change from baseline in HAMA score. By-visit analyses of data pooled across studies revealed significantly greater improvement (p<0.05) in the escitalopram group beginning at week 1 or 2 and continuing through week 8 for all primary and secondary efficacy variables. The mean change in HAMA total score from baseline to endpoint also was significantly greater for patients maintained at escitalopram 10 mg/day than for those receiving placebo. Escitalopram was generally well tolerated., Limitations: The studies included in this analysis were of short-term duration and excluded patients with significant medical and psychiatric comorbidities, such as major depressive disorder., Conclusion: Results from the individual trials and the pooled analysis demonstrate that escitalopram is effective and well tolerated for the treatment of GAD.

This study examined the psychometric properties of the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS; Scahill et al., 1997). Participants were 82 children and adolescents diagnosed with obsessive-compulsive disorder (OCD). Confirmatory factor analyses of 2 previously found models (Obsessions and Compulsions; Disturbance and Severity) yielded poor fit indexes. Exploratory factor analysis supported a model of severity and disturbance with slightly different item content than found by McKay et al. (2003). The internal consistency of the factors was acceptable, and the convergent and divergent validity was supported vis-a-vis correlations with clinician ratings of impairment, self-report measures of depression and anxiety, and parent ratings of Tourette's disorder (TD) symptoms. These findings suggest that the CY-BOCS Total Score may represent an inaccurate assessment of symptom severity and supports the use of the revised Severity and Disturbance factors in assessing illness severity.

Background: Generalized anxiety disorder (GAD) is characterized by anxiety, and also frequently associated with depressive symptoms. Benzodiazepines have commonly been used in the treatment of GAD, but are not effective antidepressant agents. In this study, we determined whether the selective serotonin reuptake inhibitor escitalopram, was effective across different subgroups and outcomes (anxious symptoms, depressive symptoms, and quality of life)., Methods: Three randomized, placebo controlled studies of escitalopram in GAD have employed a similar design, allowing for pooling of the data. The primary efficacy measure was the Hamilton Anxiety Scale (HAMA). General linear models were used to determine the efficacy of escitalopram across different subgroups and outcomes., Results: Escitalopram was efficacious for GAD on a range of measures of both anxiety and depression, and improved the associated impairment in quality of life. There was no significant interaction of effects on the HAMA with demographic or clinical variables. Furthermore, escitalopram was efficacious on both primary and secondary scales in the subgroup of subjects with above-median severity of depressive symptoms at baseline (HAMD-17 > 12)., Conclusions: Escitalopram reduces anxiety and depressive symptoms in GAD, and improves quality of life. It is equally effective in GAD patients, with an above-median level of depressive symptoms. Further research is needed to determine whether these results can be extrapolated to GAD patients with comorbid major depression.

The factor structure of the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) has been examined in a number of prior investigations; however, findings have not consistently yielded a stable factor solution. The present study therefore tested the fit of each previously reported factor structure. One hundred thirty-one adults with obsessive-compulsive disorder (OCD) were administered the Y-BOCS; a portion of these participants completed self-report measures of depression and obsessive-compulsive symptoms and were rated on a global impairment index. Consistent with the originally proposed structure, confirmatory factor analyses supported a factor structure comprised of obsession and compulsion factors. Reliability and convergent validity of these factors were generally satisfactory, although divergent validity was not entirely supported. Implications of these findings on scoring the Y-BOCS are discussed., ((c) 2005 Wiley-Liss, Inc.)

This study evaluated the psychometric properties of the Tourette's Disorder Scale-Parent Rated (TODS-PR), a 15-item parent-rated instrument that assesses a range of common symptoms seen in childhood Tourette's Disorder (TD) patients including tics, obsessions, compulsions, inattention, hyperactivity, aggression, and emotional disturbances. Participants were 67 children and adolescents ages 6-17 years who were diagnosed with TD and/or OCD and seen as a part of a larger study. Confirmatory factor analyses supported the original 4-factor structure of the TODS-PR with some slight re-specification of factor content. Internal consistencies were acceptable for the TODS-PR Total Score and factors. The TODS-PR Total Score and factors showed good convergent validity with other measures of symptomatology and impairment. These findings suggest that the TODS-PR is a reliable and valid parent-rating scale for assessing TD symptoms.

This study evaluated the psychometric properties of the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS). A total of 61 children and adolescents, aged 4-18 years, who were diagnosed with obsessive-compulsive disorder (OCD) participated. Thirty-seven of these children also participated in a second CY-BOCS administration by the same rater an average of 41 days later. Good internal consistency and test-retest reliability were found for the CY-BOCS Obsession and Compulsion Severity Scores and the Total Score. CY-BOCS scores demonstrated strong correlations with clinician-rated measures of impairment, obsessions, and compulsions. In addition, CY-BOCS scores were moderately related to measures of depression, aggressive behavior, and symptoms of attention deficit hyperactivity disorder, but were not significantly related to clinician ratings of tics or self-reports of general anxiety. Findings suggest that the CY-BOCS is a reliable and valid instrument for the assessment of childhood obsessions and compulsions.

Although previous functional brain imaging studies have found that the insula responds selectively to facial expressions of disgust, it remains unclear whether the insula responds selectively to disgust-inducing pictures. In this fMRI study, healthy volunteers viewed pictures of contamination, human mutilation, attacks and neutral scenes during scanning, and then rated pictures for the 'basic' emotions. The anterior insula responded to contamination and mutilation but not attacks, while the ventral visual areas responded to attacks and mutilations more strongly than contamination. The above activations were predicted by disgust and arousal ratings respectively. Additionally, mutilations uniquely activated the right superior parietal cortex. These results support selective disgust processing at the insula, and suggest distinct neural responses to contamination and mutilation.

Objective: To describe smiling and euphoria induced by deep brain stimulation (DBS)., Background and Significance: The brain systems inducing emotional experiences and displays are not entirely known, but the ventral striatum including the nucleus accumbens has been posited to play a critical role in mediating emotions with positive valence. DBS has been successfully employed for the treatment of movement disorders, and most recently obsessive compulsive disorder (OCD). The purpose of this report is to describe the emotional changes associated with stimulation of the ventral striatum., Methods: A single patient with intractable OCD had electrode arrays placed in the right and left anterior limbs of the internal capsule and region of the nucleus accumbens. Changes in facial movement during stimulation were quantified by video recording. Ten video segments, time locked to the onset of stimulation, were digitized and changes in pixel intensity that occurred over both sides of the lower face, on a frame by frame basis, following stimulation onset were computed. These summed changes in pixel intensity represented the dependent variable of "entropy" and directly corresponded to changes in light reflectance that occur during facial movement., Results: During stimulation on both the right and left side, the patient consistently developed a half smile on the side of the face contralateral to the stimulating electrode, and also became euphoric. The effect ceased when DBS was discontinued., Conclusions: DBS in the region of the nucleus accumbens produced smile and euphoria suggesting that alterations in the ventral striatum may result in emotional experience and displays. We hypothesize the existence of a limbic-motor network responsible for such changes. This observation suggests that DBS may be useful as a therapy for mood disorders.

Prader-Willi syndrome is a multisystem neurogenetic obesity disorder with behavioral manifestations, including hyperphagia, compulsive behavior, self-injury, and mild to moderate mental retardation. In an 8-week open-label study, we evaluated adjunctive therapy with the anticonvulsant topiramate in 8 adults with Prader-Willi syndrome. Appetite was measured by a 1-hour access to food four times throughout the study and quantified with a visual analogue scale. Topiramate did not significantly change calories consumed, Body Mass Index, or increase self-reported appetite. In addition, there were no significant changes in compulsions. Surprisingly, topiramate treatment resulted in a clinically significant improvement in the self-injury (i.e., skin-picking) that is characteristic of this syndrome. Potential benefits of topiramate for self-injury should be evaluated further in controlled trials.

Background: One of the few combination approaches to the treatment of obsessive-compulsive disorder (OCD) with encouraging support is the addition of an antipsychotic to a serotonin reuptake inhibitor., Methods: The study consisted of a 6-week, placebo-controlled addition of olanzapine 5-10 mg (6.1 +/- 2.1 mg, mean +/- SD) to fluoxetine in OCD subjects who were partial or nonresponders to an 8-week, open-label fluoxetine trial (40 mg in 43 subjects, 20 mg in 1 subject)., Results: Both the fluoxetine-plus-olanzapine (n = 22) and fluoxetine-plus-placebo (n = 22) groups improved significantly over 6 weeks [F(3,113) = 11.64, p <.0001] according to Yale-Brown Obsessive Compulsive Scale scores with repeated-measures analysis of variance; however, the treatment x time interaction was not significant for olanzapine versus placebo addition to fluoxetine., Conclusions: These findings indicate no additional advantage of adding olanzapine for 6 weeks in OCD patients who have not had a satisfactory response to fluoxetine for 8 weeks, compared with extending the monotherapy trial.

Serotonin reuptake inhibitors (SRIs), especially potent ones given at high doses over long periods of time, are often effective in the treatment of obsessive-compulsive disorder (OCD). However, a large percentage of patients do not respond to treatment with SRIs, and those who do respond often do not fully remit, which should be the standard goal of treatment in OCD. If a patient has been treated for several months and has not yet responded to treatment with several SRIs, the physician should perform a careful assessment of resistant and/or residual clinical symptoms and any comorbid conditions to determine which next-step treatment would be the most appropriate. One strategy for patients who have not responded to treatment with an SRI is to switch them to a serotonin-norepinephrine reuptake inhibitor, because some patients may respond better to agents that target multiple systems. Another promising approach is the augmentation of SRIs with neuroleptics. In addition, open trials have shown that intravenous (IV) clomipramine and IV citalopram may be effective in the treatment of resistant OCD. Novel pharmacotherapeutic treatments and electroconvulsive therapy have been attempted, with mixed success. Recently, researchers have been studying repetitive transcranial magnetic stimulation, vagal nerve stimulation, and neurosurgical approaches such as gamma knife capsulotomy and deep brain stimulation to learn if these procedures are effective in treating treatment-resistant OCD. Repetitive transcranial magnetic stimulation has possibilities not only as a therapy but also as an instrument that can help researchers describe the neurocircuitries involved in OCD. More results are needed before the effectiveness of the nonpharmacologic treatments for OCD can be determined.

Background: A subgroup of children with obsessive-compulsive and tic disorders are proposed to have an infectious trigger. The purpose of this study was to investigate the relationship between group A streptococcal titers and symptom fluctuations in children with a clinical course resembling that described for pediatric autoimmune neuropsychiatric disorders associated with streptococcus., Methods: Twenty-five children with obsessive-compulsive disorder and/or tic disorder were evaluated for neuropsychiatric severity and group A streptococcal antibody titers (streptolysin O, deoxyribonuclease B, and carbohydrate A) at 6-week intervals for > or = six consecutive evaluations (total visits=277)., Results: Children with large symptom fluctuations (n=15) were compared with children without dramatic fluctuations (n=10). Co-movements of obsessive-compulsive/tic severity and group A streptococcal antibodies were assessed. In subjects with large symptom changes, positive correlations were found between streptococcal titers and obsessive-compulsive severity rating changes (p=.0130). These subjects were also more likely to have elevated group A streptococcal titers during the majority of observations (p=.001). Tic symptom exacerbations occurred more often in the fall/winter months than spring/summer months (p=.03)., Conclusions: Patients with marked obsessive-compulsive/tic symptom changes may be characterized by streptococcal titer elevations and exhibit evidence of seasonal tic exacerbations.

Selection of appropriate treatment for generalized anxiety disorder (GAD) is influenced by several considerations, including psychiatric comorbidity. Emerging data suggest that GAD has a chronic course and a high comorbidity with depression. Successful treatment can be facilitated by first establishing treatment goals, which include managing acute anxiety and following through to remission. Prevention of GAD recurrence should be the ultimate objective. Many treatments exist to aid in the realization of treatment goals, including benzodiazepines, hydroxyzine, buspirone, selective serotonin reuptake inhibitors (SSRIs), and serotonin-norepinephrine reuptake inhibitors (SNRIs). Some SSRIs and an SNRI have been demonstrated effective in both acute and long-term trials, establishing them as first-line therapies. Benzodiazepines are helpful because of their rapid onset of action and efficacy in somatic and autonomic symptoms of GAD. Other medications in the pipeline include gamma-aminobutyric acid (GABA) modulators, which may have lower abuse potential than currently available agents that act at the GABA receptor; corticotropin-releasing hormone (CRH) antagonists; and pregabalin. The recent realization of the chronic nature of GAD and the recognition of its frequent comorbidity with depression, coupled with data from randomized clinical trials of newer generation agents, should help physicians better diagnose GAD and achieve the goal of bringing patients to full remission.

Background: There is growing interest in the role of disgust in the pathogenesis of obsessive-compulsive disorder (OCD)., Methods: Eight OCD subjects with contamination preoccupations and eight gender- and age-matched healthy volunteers viewed pictures from the International Affective Picture System during functional magnetic resonance imaging scans., Results: A different distribution of brain activations was found during disgust-inducing visual stimulation in several areas, most notably the insula, compared with neutral stimulation in both OCD subjects and healthy volunteers. Furthermore, whereas activation during the threat-inducing task in OCD subjects showed a pattern similar to that in healthy volunteers, the pattern of activation during the disgust-inducing task was significantly different, including greater increases in the right insula, parahippocampal region, and inferior frontal sites., Conclusions: This pilot study supports the relevance of disgust in the neurocircuitry of OCD with contamination-preoccupation symptoms; future studies looking at non-OCD individuals with high disgust ratings, non-contamination-preoccupied OCD individuals, and individuals with other anxiety disorders are needed.

Objective: The aim of this 12-week, double-blind, flexible-dose, placebo-controlled, parallel-arm, multicenter trial was to determine the safety and efficacy of fluvoxamine in a controlled-release (CR) formulation in adult outpatients with obsessive-compulsive disorder (OCD)., Method: 253 adult outpatients with DSM-IV OCD were randomly assigned to receive 100 to 300 mg of fluvoxamine CR (N = 127) or placebo (N = 126) once daily for 12 weeks. Intent-to-treat analyses of efficacy assessments with the Yale-Brown Obsessive Compulsive Scale (YBOCS), Clinical Global Impressions-Severity of Illness scale (CGI-S), and Clinical Global Impressions-Improvement scale (CGI-I) were conducted., Results: Fluvoxamine CR was significantly (p <.05) superior to placebo in decreasing YBOCS total score beginning at week 2. This early response was sustained at all subsequent visits. At endpoint, there was a mean decrease of 8.5 +/- 0.7 (31.7%) in the YBOCS total score compared with baseline in the fluvoxamine CR treatment group versus a mean decrease of 5.6 +/- 0.7 (21.2%) in the placebo group (p =.001). Fluvoxamine CR was also significantly superior to placebo in lowering the severity of illness (CGI-S, p =.002) and in producing clinical improvement (CGI-I, p <.01). At endpoint, significantly greater percentages of the fluvoxamine CR treatment group were responders (p =.002) and remitters (p =.019) compared with the placebo group., Conclusion: Over 12 weeks, fluvoxamine CR treatment was associated with a statistically significant and clinically relevant reduction in OCD severity and was found to be safe and well tolerated. The early onset of therapeutic effect, starting from week 2, was of particular interest.

Objective: To elucidate the neural mechanisms of depression., Background: Despite extensive study, the neurophysiology of the brain's state(s) corresponding to depression remains uncertain., Methods: HMPAO single photon emission computed tomographic (SPECT) scans were obtained from eight adults diagnosed with major depression resistant to medication (average age 51 years; 4 men) before and immediately after 10 days of 20 Hz repetitive transcranial magnetic stimulation (rTMS) (2000 stimuli/daily 30' treatment). To maximize the likelihood that SPECT scans reflected the state of depression, rather than uncontrolled responses of patients to poorly constrained environments, HMPAO was administered while subjects performed a simple task involving continuous monitoring of the direction of a large arrow on a computer screen and continuously tapping with the left or right index finger according to the direction of the arrow. Mean baseline Beck Depression Inventory (BDI) score was 27.4 (SD = 8.3) and mean posttreatment BDI score was 17.5 (SD = 8.5)., Results: Treatment responders (defined by reduction in BDI score of > or = 30%) had significantly less pretreatment blood flow in the left amygdala compared with nonresponders. Responders demonstrated two patterns of change in regional blood flow with treatment: a reduction in orbitofrontal blood flow and/or a reduction in anterior cingulate blood flow. Nonresponders did not demonstrate any regional changes in blood flow with treatment., Conclusions: These results suggest that there may be either more than one state of depression, or that depression may be associated with more than one pattern of psychologic activity, which in turn defines the depressive experience for individual patients.

Self-injurious behaviour (SIB), most notably skin picking, has been described by various terms in the literature ranging from neurotic/psychogenic excoriations to compulsive/pathological skin picking. Prader-Willi Syndrome (PWS) is a neurogenetic multisystem disorder characterized by infantile hypotonia, mental retardation, short stature, hypogonadism, dysmorphic features, and hyperphagia with a high risk of obesity. Psychiatric manifestations include SIBs in the form of skin picking, nail biting and rectal gouging. Topiramate is a novel anti-epileptic medication without significant liability of weight gain. There are no published reports of topiramate being utilized in PWS or SIB. We report attenuation of SIB with resultant lesion healing in three PWS adults treated with topiramate in an 8-wk open-label trial. Although our findings should be treated with caution, they suggest that double-blind or cross-over studies with topiramate are warranted to establish the possible role of topiramate in attenuating SIB in PWS and other disorders that involve SIB.

Objective: Little is known about the longitudinal course of symptoms in adult patients with obsessive-compulsive disorder (OCD), although some evidence exists regarding symptom stability in children and adolescents. This study systematically investigated the temporal stability of individual symptoms and symptom dimensions of OCD in adult patients who were followed prospectively for 2 years., Method: One hundred seventeen adult outpatients with OCD from three U.S. sites were administered the Yale-Brown Obsessive Compulsive Scale symptom checklist four times over a period of 2 years. Eighty-one (69%), 83 (71%), and 67 (57%) patients were available 6 months, 1 year, and 2 years after initial screening, respectively. Different analytic methods assessed the stability of OCD symptoms within and between previously identified symptom dimensions., Results: For the most part, patients maintained their symptoms throughout follow-up, although some symptoms were more stable than others. For the symptoms that changed, changes occurred within rather than between symptom dimensions; qualitative shifts from one dimension to another were rare. The strongest predictor of the presence of a particular symptom was having had that symptom in the past. Although most patients had received pharmacological and behavioral treatment during the follow-up period, changes within symptom dimensions could not be explained by overall clinical improvement over time., Conclusions: Symptoms of adult patients with OCD might be more stable across time than previously thought, with some symptoms waxing and waning within symptom dimensions and rarely involving shifts between dimensions. Longer follow-up studies involving larger samples are needed to better understand the fluctuations of OCD symptoms across time.

Background: Previous research has suggested that a subgroup of children with obsessive compulsive disorder (OCD) have neuropsychiatric sequelae of streptococcal pharyngitis, similar to that seen in the neurological manifestation of rheumatic fever (RF). Monoclonal antibody D8/17 demonstrates increased binding to B cells in patients with RF and in patients with neuropsychiatric disorders using immunofluorescent microscopy., Objective: The aim of this study was to determine if an earlier immunofluorescent microscopy study of monoclonal antibody D8/17 in childhood-onset OCD and/or chronic tic disorder (CTD) could be replicated using the more objective method of flow cytometric analysis., Method: D8/17 binding to B cells was determined in patients with OCD and or CTD (N=32), and healthy controls (N=12) by flow cytometric analysis., Results: Subjects with OCD/CTD showed increased mean cell binding (26.0%) of monoclonal antibody compared with healthy controls (9.1%) (p<0.001). When using the threshold of greater than 19% binding (95% upper confidence interval) as a measure of positivity, 65.6% of patients compared with 8.3% of controls showed increased antibody binding to B cells (p=0.01)., Conclusions: Although this study reports positive results, many methodological issues will need to be addressed before generalized use of assay for diagnostic purposes.

During the last few years, an increased interest in the possibility of immune mediated pathophysiology of obsessive compulsive disorder (OCD) and related disorders has been seen. In the late 1980s, the National Institute of Mental Health reported an increase of obsessive compulsive symptoms in patients with Sydenham chorea (SC). Subsequently, a precipitating streptococcal infection in children with sudden onset of OCD symptoms but no chorea led to the coining of PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcus). This association has furthered interest in studying immune parameters in non-PANDAS OCD as well. This article will review the neuropsychiatric findings in OCD and Tourette syndrome (TS) with emphasis placed on PANDAS, and its association with SC, and a review of the existing studies that have assessed immunologic measures in patients with OCD and TS., (Copyright 2001 by W.B. Saunders Company)

Psychobiologic models of obsessive-compulsive disorder (OCD) have focused on cortico-striatal-thalamic-cortical (CTSC) circuits, noting normal function in cognitive and motoric procedural strategies. Such models have relied on the classification of OCD as an anxiety disorder, seldom exploring other relevant emotions. Based on the hypothesis that a central emotion in OCD is disgust, the authors review the literature on its psychobiology and its relevance to current models of OCD. There are important parallels between the psychobiology of OCD and that of disgust. Obsessive- compulsive disorder may be conceptualized in terms of a false contamination alarm in which disgust plays a crucial organizing or embodying role, not only at a basic brain level, but also in terms of the psychosocial aspects of the disorder. Just as psychobiologic models of panic disorder and post- traumatic stress disorder have been strengthened by the inclusion of preclinical work on amygdala-mediated fear conditioning, so findings on disgust and its mediating CSTC circuits may generate useful hypotheses for OCD research.

There is substantial evidence that obsessive-compulsive disorder (OCD) is mediated by specific cortico-striatal- thalamic-cortical (CTSC) circuits. Here we discuss very recent publications that address the following questions: How does damage to CSTC circuitry come about?; What are the neurochemical systems involved in mediating this circuitry?; and What are the implications of such damage for understanding the pathogenesis and management of OCD? A cognitive-affective neuroscience perspective is helpful in advancing our understanding of the role of these circuits in OCD and the dysfunctional procedural strategies that appear to characterize this disorder. Furthermore, this model is becoming integrated with a range of data including brain imaging, genetic, immunologic, and neurochemical findings.

Sydenham's chorea (SC) is a major manifestation of rheumatic fever characterized by an array of neuropsychiatric symptoms that vary in severity, timing, and character. Some of the same symptoms are seen in Tourette's syndrome and childhood-onset obsessive-compulsive disorder. Genetic vulnerability appears to play a role in all three conditions. The term PANDAS (pediatric autoimmune neuropsychiatric disorder associated with streptococcus) has been introduced to describe a putative subset of obsessive-compulsive disorder and Tourette's syndrome that bears some resemblance to Sydenham's chorea. This article discusses whether PANDAS should be subsumed under Sydenham's chorea, thus expanding the diagnostic boundaries of Sydenham's chorea to include primarily neuropsychiatric presentations now classified as cases of obsessive-compulsive disorder or Tourette's syndrome. We conclude that PANDAS is a useful construct, but that it would be premature to view it as a subset of Sydenham's chorea-whether defined narrowly or broadly.

Obsessive-compulsive disorder (OCD) is a complex psychiatric disorder characterized by recurring obsessions or compulsions that cause significant distress to the patient or significantly interfere with the patient's normal home, work, or social activities [Diagnostic and Statistical Manual of Mental Disorders, 4th Edition. Washington, DC: American Psychiatric Association, 1994]. Twin and family studies have suggested that OCD has a significant genetic component. We performed complex segregation analyses using POINTER with families ascertained through an OCD-affected proband. In an attempt to resolve the phenotypic heterogeneity observed among individuals with OCD these segregation analyses used four factor-analytic symptom dimensions to subset the family sample based upon probands' symptom factor scores. Analysis of the entire sample allowed rejection of only the no transmission model; that model was also rejected in all subsequent analyses. Limiting the analyses to families with at least one OCD-affected member in addition to the proband (the demonstrably familial form of OCD) allowed rejection of all models except the mixed model. Analyses limited to families of high-factor-3 (symmetry and ordering symptoms) probands led to rejection of the polygenic model, indicating the involvement of a major locus. Additionally, the relative risk of OCD or subclinical OCD was 1.7 for relatives of probands with a factor 3 score greater than zero compared with relatives of probands with a low factor score. The symptoms attributed to high factor 3 scores (symmetry and ordering) may constitute a genetically significant symptomatic subtype of OCD. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:669-675, 1999., (Copyright 1999 Wiley-Liss, Inc.)