Dianne M. Hezel

A Single-Blinded Case-Control Study of Memantine in Severe Obsessive-Compulsive Disorder

Background: Obsessive-compulsive disorder (OCD) is a common debilitating psychiatric illness that typically improves but does not remit with first-line medication and behavioral treatments. Serotonergic agents including selective serotonin reuptake inhibitors and clomipramine have provided the mainstay of OCD medication management for decades. Combined dopamine/serotonergic agents such as atypical antipsychotics are presently the only OCD-augmenting strategies proven effective via randomized controlled trials. Despite increasing evidence for a pathogenic role of glutamate in OCD, no controlled trials of glutamatergic augmenting agents have been reported. Methods: An intent-to-treat sample included 44 subjects receiving standard treatment at the McLean/Massachusetts General Hospital Intensive Residential Treatment (IRT) program, 22 of whom also received memantine augmentation. Admission, monthly and discharge measures of OCD, depression, and psychosocial functioning were collected by raters blinded to augmentation status. Matched controls were selected based on sex, initial OCD severity, psychosocial functioning, and timing of admission. The Clinical Global Improvement Scale captured global clinical change. Results: Mean (SD) Yale-Brown Obsessive Compulsive Scale score decreases were 7.2 (6.4) among the cases and 4.6 (5.9) among the matched controls, reflecting mean clinical improvement among the cases (27.0% decrease) but not the controls (16.5% decrease). Mean (SD) depression severity score decreases were 5.8 (9.5) among the cases and 4.7 (9.9) among the controls. Initial intrusive obsessions were significantly more severe among marked responders compared with limited response or nonresponse cases (4.4 vs 2.9; t = 2.15; P = 0.048). Conclusions: This study provides preliminary supportive evidence for the effectiveness of memantine as a glutamatergic augmenting agent in severe OCD. Future randomized double-blind placebo-controlled trials are warranted.

Cognitive Inflexibility and Frontal-Cortical Activation in Pediatric Obsessive-Compulsive Disorder

OBJECTIVE Deficits in cognitive flexibility and response inhibition have been linked to perturbations in cortico-striatal-thalamic circuitry in adult obsessive-compulsive disorder (OCD). Although similar cognitive deficits have been identified in pediatric OCD, few neuroimaging studies have been conducted to examine its neural correlates in the developing brain. In this study, we tested hypotheses regarding group differences in the behavioral and neural correlates of cognitive flexibility in a pediatric OCD and a healthy comparison (HC) sample. METHOD In this functional magnetic resonance imaging (fMRI) study, a pediatric sample of 10- to 17-year-old subjects, 15 with OCD and 20 HC, completed a set-shifting task. The task, requiring an extradimensional shift to identify a target, examines cognitive flexibility. Within each block, the dimension (color or shape) that identified the target either alternated (i.e., mixed) or remained unchanged (i.e., repeated). RESULTS Compared with the HC group, the OCD group tended to be slower to respond to trials within mixed blocks. Compared with the HC group, the OCD group exhibited less left inferior frontal gyrus/BA47 activation in the set-shifting contrast (i.e., HC > OCD, mixed versus repeated); only the HC group exhibited significant activation in this region. The correlation between set shifting-induced right caudate activation and shift cost (i.e., reaction time differential in response to mixed versus repeated trials) was significantly different between HC and OCD groups, in that we found a positive correlation in HC and a negative correlation in OCD. CONCLUSIONS In pediatric OCD, less fronto-striatal activation may explain previously identified deficits in shifting cognitive sets.

Development and Psychometric Properties of the OCD Family Functioning (OFF) Scale

Obsessive-compulsive disorder (OCD) influences not only patients but also family members. Although the construct of family accommodation has received attention in OCD literature, no measures of overall family functioning are currently available. The OCD Family Functioning (OFF) Scale was developed to explore the context, extent, and perspectives of functional impairment in families affected by OCD. It is a three-part, self-report measure capturing independent perspectives of patients and relatives. A total of 400 subjects were enrolled between 2008 and 2010 from specialized OCD clinics and OCD research studies. Psychometric properties of this scale were examined including internal consistency, test-retest reliability, convergent and divergent validity, and exploratory factor analyses. Both patient and relative versions of the OFF Scale demonstrated excellent internal consistency (Cronbachs alpha coefficient = 0.96). The test-retest reliability was also adequate (ICC = 0.80). Factor analyses determined that the OFF Scale comprises a family functioning impairment factor and four OCD symptom factors that were consistent with previously reported OCD symptom dimension studies. The OFF Scale demonstrated excellent convergent validity with the Family Accommodation Scale and the Work and Social Adjustment Scale. Information gathered regarding emotional impact and family role-specific impairment was novel and not captured by other examined scales. The OFF Scale is a reliable and valid instrument for the clinical and research assessment of family functioning in pediatric and adult OCD. This will facilitate the exploration of family functioning impairment as a potential risk factor, as a moderator and as a treatment outcome measure in OCD.

A Theoretical review of cognitive biases and deficits in obsessive–compulsive disorder

During the past 30 years, experimental psychopathologists have conducted many studies aiming to elucidate the cognitive abnormalities that may figure in the etiology and maintenance of OCD. In this paper, we review research on both dysfunctional beliefs and cognitive deficits in OCD, as findings from both traditional self-report and information-processing approaches provide distinct sources of information concerning cognitive abnormalities. First, we discuss dysfunctional beliefs and metacognitive beliefs implicated in the disorder. Research has identified a number of maladaptive appraisals (e.g., heightened responsibility) and metacognitive beliefs (e.g., need to control ones thoughts) that are associated with the disorder, yet these are not invariably present in all cases of OCD. Next, we review the literature on memory and attentional deficits and biases in OCD. This line of research shows inconsistent evidence for deficits in memorial and attentional processes, but does indicate that people with the disorder have memory and attention biases that may be related to metacognitive beliefs about their ability to remember and attend to stimuli. Finally, we discuss recent work that suggests that people with OCD have reduced access to internal states, thus causing them to engage in rituals to resolve persistent uncertainty. Implications and future directions are discussed.

Emotional distress and pain tolerance in obsessive-compulsive disorder

BACKGROUND AND OBJECTIVES Physical pain can reduce emotional distress, perhaps especially the psychic pain of guilt. This implies that people who continually experience guilt may exhibit greater tolerance for pain relative to people who do not. METHODS To test this hypothesis, we administered a pressure algometer procedure to assess pain tolerance in patients with obsessive-compulsive disorder (OCD) plagued by moral obsessions (e.g., concerns about harming others, violating religious values), in patients with OCD with non-moral obsessions (e.g., regarding contamination and symmetry), and in healthy comparison subjects. RESULTS The results indicated that the OCD groups did not differ in levels of guilt, emotional distress tolerance, or in pain endurance. However, when we collapsed across subtypes, OCD subjects endured pain significantly longer than did healthy subjects. LIMITATIONS Limitations included small sample size and use of a sample with complex OCD symptoms that were, in some instances, difficult to categorize. CONCLUSIONS The results suggest that individuals with severe OCD might be willing to endure physical pain as a distraction from emotional distress, an expression of negative self-worth, or as a means to gain control over some aspect of suffering.

Long-term outcome following Intensive Residential Treatment of Obsessive–Compulsive Disorder

BACKGROUND IRT has been demonstrated as an effective treatment for severe, refractory OCD. METHODS Consecutive IRT subjects were ascertained over a 12 month period (female N=26, male N=35). Psychometric measures were completed at admission and discharge from the McLean/MGH OCD Institute IRT, including the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), Beck Depression Inventory (BDI) and the Work and Social Adjustment Scale (WSA)(N=61). These measures were repeated at one (N=57), three (N=42) and six months (N=36) following discharge. This study was IRB approved. RESULTS OCD mean severity did not significantly worsen from discharge to the one (17.4, SD 6.5), three (16.5, SD 7.4) or six month (16.2, SD 7.3) follow-up (p>0.25). Furthermore, the significant improvement from admission was maintained at each of the one (17.4, SD 6.5), three (16.5, SD 7.4) and six month (16.2, SD SD 7.3) follow-up time points (p<0.001). Relapsers were significantly more likely to be living alone following discharge (p=0.01), and were less likely to have comorbid illnesses (p=0.02). There were no significant differences found between study dropouts and completers with regards to YBOCS scores (P>0.47). CONCLUSION In the first OCD IRT long-term follow-up study to date, findings have indicated that mean treatment gains were maintained at one, three, and six months post-discharge. This finding is important as it suggests that improvements of OCD severity were subsequently retained in home and work environments. Improvement of depression severity from admission was also maintained.

Creativity, personality, and hoarding behavior

Compulsive hoarding is a debilitating illness that is characterized by excessive collection of and failure to discard items, irrespective of their uselessness or hazardousness. Anecdotal evidence suggests that individuals who hoard may be more creative than individuals without hoarding behavior; however, this hypothesis has never been tested empirically. In the present study, we examined the relationship between hoarding symptoms and performance on a series of creativity measures. We also explored the extent to which hoarding symptoms were associated with factors such as personality, impulsivity, distress tolerance, and attitudes about money and the environment. Our findings revealed no significant associations between hoarding behavior and any measure of creativity. Hoarding behavior was also unrelated to attitudes about money or concern about the environment. However, consistent with previous research, hoarding tendencies were correlated with higher levels of neuroticism and impulsivity, as well as with lower levels of conscientiousness and distress tolerance. Implications of these findings are discussed.

Assessment and Medication Management of Paediatric Obsessive-Compulsive Disorder

Paediatric obsessive-compulsive disorder (OCD) is a common, yet under-recognized, neuropsychiatric illness in both clinical and community settings. Symptoms tend to be hidden or misunderstood by affected youth, and parents may inadvertently accommodate OCD, thus worsening its severity. These symptoms may include compulsive reassurance seeking, confessing and ‘just right’ rituals, in addition to more classic OCD behaviours. Fortunately, numerous psychometric measures are available to assist in clinical assessment of this disorder and its sequelae. Once properly diagnosed, paediatric OCD is highly treatable with empirically proven approaches including cognitive-behaviour therapy (CBT) and serotonin reuptake inhibitor (SRI) medications. Clinically meaningful symptom improvement is the norm following these strategies, although full remission is not, as symptoms tend to wax and wane over time. Paediatric OCD is highly co-morbid with other anxiety disorders, tic disorders, depression and attention-deficit hyperactivity disorder, which also require specific attention. For moderate to severe OCD, an interdisciplinary approach combining individual and family CBT with SRI trials is recommended. For severe treatment-refractory illness, early evidence supports the benefit of augmenting agents, such as atypical antipsychotics and potentially those with glutamatergic activity. Clinical outcome assessment in paediatric OCD should always include broad domains of individual and family functioning, in addition to symptom improvement.