Meta-analysis of association between obsessive-compulsive disorder and the 3' region of neuronal glutamate transporter gene SLC1A1.

The neuronal glutamate transporter gene SLC1A1 is a candidate gene for obsessive-compulsive disorder (OCD) based on linkage studies and convergent evidence implicating glutamate in OCD etiology. The 3' end of SLC1A1 is the only genomic region with consistently demonstrated OCD association, especially when analyzing male-only probands. However, specific allele associations have not been consistently replicated, and recent OCD genome-wide association and meta-analysis studies have not incorporated all previously associated SLC1A1 SNPs. To clarify the nature of association between SLC1A1 and OCD, pooled analysis was performed on all available relevant raw study data, comprising a final sample of 815 trios, 306 cases and 634 controls. This revealed weak association between OCD and one of nine tested SLC1A1 polymorphisms (rs301443; uncorrected P = 0.046; non-significant corrected P). Secondary analyses of male-affecteds only (N = 358 trios and 133 cases) demonstrated modest association between OCD and a different SNP (rs12682807; uncorrected P = 0.012; non-significant corrected P). Findings of this meta-analysis are consistent with the trend of previous candidate gene studies in psychiatry and do not clarify the putative role of SLC1A1 in OCD pathophysiology. Nonetheless, it may be important to further examine the potential associations demonstrated in this amalgamated sample, especially since the SNPs with modest associations were not included in the more highly powered recent GWAS or in a past meta-analysis including five SLC1A1 polymorphisms. This study underscores the need for much larger sample sizes in future genetic association studies and suggests that next-generation sequencing may be beneficial in examining the potential role of rare variants in OCD.

The Skin Picking Impact Scale (SPIS): scale development and psychometric analyses.

The Skin Picking Impact Scale (SPIS) is a self-report instrument developed to assess the psychosocial consequences of repetitive skin picking. An initial 28-item scale was administered to 31 individuals with severe self-injurious skin picking and 78 individuals with non-self-injurious skin picking. Item difficulty levels and part-whole correlations resulted in a 10-item scale with good internal consistency. SPIS scores for those with self-injurious skin picking were significantly higher than for those with non-self-injurious skin picking. SPIS scores for those with self-injurious skin picking correlated with duration of daily picking, satisfaction during picking, and shame subsequent to picking, as well as Beck Depression Inventory and Beck Anxiety Inventory scores. Sensitivity and specificity analyses indicate that a scale cutoff score of 7 optimally discriminates individuals with self-injurious skin picking from those with non-self-injurious skin picking.

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

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

Home-based behavior therapy for obsessive-compulsive disorder: a case series with data.

The effectiveness of "home-based" exposure and response prevention was assessed in a series of 11 subjects with obsessive-compulsive disorder (OCD). Patients received 24 treatment sessions in a range of natural settings and situations. Sixty-four percent of the patients responded to behavior therapy in these settings, and 36% achieved lasting improvements in their OCD symptoms. Implications for the impact on consumers of this seldom-used application of behavior therapy are discussed and some recommendations for future research are made.

Probing striato-thalamic function in obsessive-compulsive disorder and Tourette syndrome using neuroimaging methods.

In summary, contemporary pathophysiological models of OCD and related disorders implicate CSTC circuitry. In this chapter, we have reviewed relevant concepts related to implicit learning and more specifically, the use of an implicit sequence learning paradigm as a probe of striato-thalamic function. An initial PET investigation of patients with OCD confirmed a priori hypotheses of failure to recruit right striatum, despite the absence of a performance deficit (22). A modified version of the SRT was studied in conjunction with fMRI and yielded reliable right-lateralized striatal activation in a cohort of 10 male subjects, with clear spatial dissociation of caudate and putamen activation foci (119). Subsequent studies in our laboratory suggest that this paradigm also yields a reliable temporal window of thalamic deactivation, and hence a means for assessing thalamic gating in human subjects (120). Finally, as presented in this chapter, preliminary data from the fMRI-SRT in patients with OCD and TS as well as normal control subjects appear to replicate and extend the findings from our original PET-SRT study in OCD. Future investigations in our laboratory will seek to elaborate upon these preliminary results. In particular, we intend to study psychiatric comparison groups to establish the generalizability and/or specificity of these findings across disorders. Within OCD, we hope to explore the relationship between abnormal brain-activation patterns and symptom dimensions (34). Further, by studying subjects with remitted OCD who have been successfully treated, we hope to determine whether the observed brain-activation abnormalities represent state or trait markers. Finally, we have already begun to test a hypothesis of parallel processing deficiency in OCD by using a dual-task version of the SRT that makes simultaneous demands on implicit and explicit information processing systems (128). It is our hope that this program of research will yield new insights about OCD and related disorders, including TS. Most importantly, as other teams of investigators pursue complementary lines of inquiry, it is our wish that collective efforts in this field will lead to improved diagnosis and treatment, if not cure or prevention, for those who are afflicted with these illnesses.

The Skin Picking Scale: scale construction and psychometric analyses.

OBJECTIVE: This paper reports on the development of the Skin Picking Scale (SPS), a six-item paper-and-pencil measure for the assessment of skin picking. METHODS: 28 severe self-injurious and 77 non-self-injurious skin pickers initially completed an eight-item severity scale modeled after the Yale--Brown Obsessive--Compulsive Scale (Y-BOCS). RESULTS: Group comparisons and part--whole correlations for individual scale items resulted in a six-item scale with a total score range of 0--24. A Cronbach's alpha coefficient of.80 indicated moderate internal consistency for the scale. Construct validity was demonstrated by significant correlations between SPS total scale scores and self-reported average duration of skin picking episodes. Significant correlations were also reported between SPS total scale scores and both Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI) scores, as well as self-reported intensity of emotions during the picking process. Lastly, sensitivity and specificity analyses suggest that a SPS cut-off score of 7 differentiates severe self-injurious and non-self-injurious skin pickers. CONCLUSION: The SPS is a valid and reliable self-report scale for the assessment of severity in medical and psychiatric patients who endorse skin picking.

An update on obsessive-compulsive disorder.

It is now recognized that obsessive-compulsive disorder (OCD) affects almost 3% of the world's population and is a major worldwide health problem. Much has been learned in the past 2 decades about the treatment of these disorders. Recent developments in neuroimaging techniques have led to a better understanding of the biology of OCD and the brain circuits that may be involved in the production of symptoms. The most effective treatment approaches, based on controlled data, are behavior therapy consisting of exposure and response prevention and specific medications. Although controversial, more invasive neurosurgical and neurostimulation approaches may hold some promise for severely disabled patients. Despite impressive research efforts, a small minority of patients remain refractory to treatment. Future clinical research should focus on this refractory group.

Longitudinal follow-up of naturalistic treatment outcome in patients with trichotillomania.

BACKGROUND: Little is known about the longitudinal course of treatment outcome in patients with trichotillomania. The authors conducted a second follow-up assessment on a cohort of hair pullers previously studied. METHOD: Forty-four subjects completed a hair-pulling questionnaire and paper-and-pencil measures of hair-pulling severity and impact, psychosocial functioning, depression, anxiety, and self-esteem. Mean time elapsed between the first and second follow-up assessment was 2.5 years (index evaluation to first follow-up = 3.5 years). RESULTS: Twenty-seven subjects (61.4%) had active treatment since the first follow-up. No significant changes in hair pulling, depression, anxiety, or psychosocial functioning were reported from first to second follow-up. Self-esteem scores significantly worsened during this period (p = .000). A trend toward worsening also existed for psychosocial impact scores. Comparison of scores at index evaluation with second follow-up still showed significant improvement over time for hair pulling (p = .001) but significant worsening in self-esteem (p = .000). Treatment and responder status were unrelated to clinical functioning, with the exception of depression and psychosocial impact. CONCLUSION: Although hair pullers exhibit initial improvement with treatment, scale scores plateau or worsen by second follow-up. Significant worsening in self-esteem at second follow-up may be related to the absence of further improvements in hair-pulling severity. Future research should focus on the interrelationships among self-esteem, depression, and hair pulling during treatment for this disorder.

Is age at symptom onset associated with severity of memory impairment in adults with obsessive-compulsive disorder?

OBJECTIVE: Age at onset is a potentially important marker for neurobiological features of obsessive-compulsive disorder (OCD). This study examined the relationship between age at symptom onset and memory impairment in adults with OCD. METHOD: The authors used the Rey-Osterrieth Complex Figure Test and the California Verbal Learning Test to compare memory functioning of 37 adult OCD patients with self-reported childhood onset of symptoms (onset at less than 18 years of age) with that of 31 patients with adult-onset symptoms. RESULTS: No differences were found between the two groups on any of the verbal and nonverbal memory measures. CONCLUSIONS: Self-reported age at symptom onset is not associated with memory performance in adult patients with OCD according to tests previously found to be sensitive to frontal-striatal system dysfunction and impairment in OCD. Such dysfunction appears to be a consistent feature of OCD in adults, regardless of age at initial symptom onset.

A magnetic resonance imaging study of regional cortical volumes following stereotactic anterior cingulotomy.

The purpose of this study was to test the hypothesis that orbitofrontal cortical volume would be reduced following anterior cingulotomy for obsessive-compulsive disorder (OCD). Whole brain cortical parcellation was performed on magnetic resonance imaging (MRI) data from nine patients, before and 9 (+/-6) months following anterior cingulotomy. No significant volumetric reductions were found in the orbitofrontal cortex. Exploratory findings of reduced volume in ventral temporo-fusiform and posterior cingulate regions were consistent with chance differences, in the face of multiple comparisons. Therefore, though the circumscribed lesions of anterior cingulotomy have recently been associated with corresponding volumetric reductions in the caudate nucleus, no comparable volumetric reductions are evident in cortical territories. Taken together, these results are most consistent with a model of cingulo-striatal perturbation as a putative mechanism for the efficacy of this procedure. While limitations in sensitivity may have also contributed to these negative findings, the methods employed have previously proven sufficient to detect cortical volumetric abnormalities in OCD. The current results may reflect a relatively diffuse pattern of cortico-cortical connections involving the neurons at the site of cingulotomy lesions. Future functional neuroimaging studies are warranted to assess possible cortical or subcortical metabolic changes associated with anterior cingulotomy, as well as predictors of treatment response.

Improvement in severe self-mutilation following limbic leucotomy: a series of 5 consecutive cases.

BACKGROUND: The efficacy of neurosurgical intervention for self-mutilation behavior associated with severe, intractable psychiatric disorders remains undetermined. We report the effects of limbic leucotomy in 5 consecutive patients with severe self-mutilation behaviors. METHOD: After unsolicited referrals from their psychiatrists and careful consideration by the Massachusetts General Hospital Cingulotomy Assessment Committee (MGH-CAC), 5 patients were treated with limbic leucotomy. Their primary DSM-IV psychiatric diagnoses were either obsessive-compulsive disorder or schizoaffective disorder. Comorbid severe, treatment-refractory self-mutilation was an additional target symptom. Outcome was measured by an independent observer using the Clinical Global Improvement. Current Global Psychiatric-Social Status Rating, and DSM-IV Global Assessment of Functioning scales in addition to telephone interviews with patients, families, their psychiatrists, and treatment teams. The mean postoperative follow-up period was 31.5 months. RESULTS: All measures indicated sustained improvement in 4 of 5 patients. In particular, there was a substantial decrease in self-mutilation behaviors. Postoperative complications were transient in nature. and postoperative compared with preoperative neuropsychological assessments revealed no clinically significant deficits. CONCLUSION: In carefully selected patients as described in this report, limbic leucotomy may be an appropriate therapeutic consideration for self-mutilation associated with severe, intractable psychiatric disorders.

Volume reduction in the caudate nucleus following stereotactic placement of lesions in the anterior cingulate cortex in humans: a morphometric magnetic resonance imaging study.

OBJECT: The goal of this study was to test hypotheses regarding changes in volume in subcortical structures following anterior cingulotomy. METHODS: Morphometric magnetic resonance (MR) imaging methods were used to assess volume reductions in subcortical regions following anterior cingulate lesioning in nine patients. Magnetic resonance imaging data obtained before and 9 +/- 6 months following anterior cingulotomy were subjected to segmentation and subcortical parcellation. Significant volume reductions were predicted and found bilaterally within the caudate nucleus, but not in the amygdala, thalamus, lenticular nuclei, or hippocampus. Subcortical parcellation revealed that the volume reduction in the caudate nucleus was principally referrable to the body, rather than the head. Furthermore, the magnitude of volume reduction in the caudate body was significantly correlated with total lesion volume. CONCLUSIONS: Taken together, these findings implicate significant connectivity between a region of anterior cingulate cortex (ACC) lesioned during cingulotomy and the caudate body. This unique data set complements published findings in nonhuman primates, and advances our knowledge regarding patterns of cortical-subcortical connectivity involving the ACC in humans. Moreover, these findings indicate changes distant from the site of anterior cingulotomy lesions that may play a role in the clinical response to this neurosurgical procedure.

Reliability and validity of a scoring system for measuring organizational approach in the Complex Figure Test.

The Rey-Osterrieth Complex Figure Test (RCFT) is a widely-used measure of visuospatial construction and nonverbal memory. One of the critical aspects of this test is that organizing the figure into meaningful perceptual units during copy enhances its subsequent free recall from memory. This study examined the psychometric properties of a new system for quantifying the organizational approach to the RCFT figure and compared it to another compatible scoring system. We investigated interrater reliability of both systems and explored the influences of copy organization and copy accuracy on immediate recall. Seventy-one participants meeting DSM-IV criteria for obsessive-compulsive disorder and 55 healthy control participants completed the copy and immediate free recall condition of the RCFT. Interrater reliability was evaluated by Kappa coefficients and Pearson correlations. The effects of copy organization and copy accuracy on immediate recall were evaluated using multiple regression analyses. Results indicated that the organizational approach could be assessed with high reliability using both scoring systems. Organization during copy was a strong predictor for subsequent free recall from memory using both approaches. Multiple regression analysis indicated that all organizational elements were not equally predictive of memory performance. This new system represents a very simple and reliable approach to scoring organization on the RCFT, since it requires the identification of only 5 figure components. These characteristics should contribute to its clinical utility.

Late-onset obsessive-compulsive disorder: a case series.

Obsessive-compulsive disorder (OCD) is a common and potentially disabling illness with onset usually in the second or third decade of life. Onset after age 50 is relatively rare and may be more likely to have an organic etiology. Out of an OCD patient population of over 1,000, the authors found 5 cases in which symptoms of OCD first developed late in life. Four of the 5 patients had intracerebral lesions in the frontal lobes and caudate nuclei, findings consistent with current theories about the pathogenesis of "idiopathic" OCD.

Relation of factor-analyzed symptom dimensions of obsessive-compulsive disorder to personality disorders.

OBJECTIVE: To assess the relation between symptom dimensions of obsessive-compulsive disorder (OCD) and comorbid personality disorders (PDs). METHOD: The scores of 75 OCD outpatients on five previously identified symptom dimensions were entered into multiple regression models as predictors of: 1) the presence of any type of PD; 2) the number of PDs; 3) the presence of any cluster A, B or C PD; and 4) the presence of each individual PD. RESULTS: Twenty-eight patients (37.3%) met criteria for one or more PDs. High scores on the 'Hoarding' dimension were strongly related to the presence of any Axis II diagnosis, and to the number of PDs. Cluster C PDs (especially obsessive-compulsive and avoidant) had the highest partial correlations with 'Hoarding'. These results were independent of OCD symptom severity. CONCLUSION: Previous conflicting findings about the prevalence of certain PDs in OCD might be due in part to differences in the constitution of the particular patient groups studied.

Characteristics of memory dysfunction in body dysmorphic disorder.

Although body dysmorphic disorder (BDD) is receiving increasing empirical attention, very little is known about neuropsychological deficits in this disorder. The current study investigated the nature of memory dysfunction in BDD, including the relationship between encoding strategies and verbal and nonverbal memory performance. We evaluated 17 patients with BDD and 17 healthy controls using the Rey-Osterrieth Complex Figure Test (RCFT) and the California Verbal Learning Test (CVLT). BDD patients differed significantly from healthy controls on verbal and nonverbal learning and memory indices. Multiple regression analyses revealed that group differences in free recall were statistically mediated by deficits in organizational strategies in the BDD cohort. These findings are similar to patterns previously observed in obsessive-compulsive disorder (OCD), suggesting a potential relationship between OCD and BDD. Studies in both groups have shown that verbal and nonverbal memory deficits are affected by impaired strategic processing.

Repetitive skin-picking in a student population and comparison with a sample of self-injurious skin-pickers.

The prevalence of skin-picking and its associated characteristics were documented in a nonclinical sample of 105 college students. Subjects completed a self-report skin-picking inventory and several paper-and-pencil scales. Students who endorsed skin-picking were compared to a clinical sample of self-injurious skin-pickers (n = 31) reported on previously. Of the student subjects, 78.1% (n = 82) endorsed some degree of skin-picking and four subjects satisfied criteria for severe, self-injurious picking. Student subjects significantly differed from the clinical sample-of self-injurious skin-pickers in the duration, focus, and extent of picking, techniques used, reasons for picking, associated emotions, and picking sequelae.

Sensory phenomena in obsessive-compulsive disorder and Tourette's disorder.

BACKGROUND: Recent studies have suggested that obsessive-compulsive disorder (OCD) is a heterogeneous disorder with some forms related to tics and Tourette's disorder. The present study was undertaken to investigate the sensory phenomena in patients with OCD and/or Tourette's disorder to determine if these phenotypic features represent valid clinical indices for differentiating tic-related OCD from non-tic-related OCD. METHOD: We evaluated 20 adult outpatients with OCD, 20 with OCD plus Tourette's disorder, and 21 with Tourette's disorder, using a semistructured interview designed to assess several definitions of sensory phenomena reported in the literature. DSM-III-R criteria were used for the OCD and Tourette's disorder diagnoses. RESULTS: Sensory phenomena including bodily sensations, mental urges, and a sense of inner tension were significantly more frequent in the 2 Tourette's disorder groups when compared with the OCD alone group. Feelings of incompleteness and a need for things to be "just right" were reported more frequently in the OCD plus Tourette's disorder group compared with the other 2 groups. CONCLUSION: Sensory phenomena may be an important phenotypic measure for grouping patients along the OCD-Tourette's disorder spectrum. Sensory phenomena include bodily and mental sensations. Bodily sensations include focal or generalized body sensations (usually tactile, muscular-skeletal/visceral, or both) occurring either before or during the patient's performance of the repetitive behaviors. These sensations are more frequently found in patients with OCD plus Tourette's disorder than in patients with OCD alone. Mental sensations include urge only, energy release (mental energy that builds up and needs to be discharged), incompleteness, and just-right perceptions. They are all more frequently found in patients with OCD plus Tourette's disorder than in patients with OCD alone.

Strategic processing and episodic memory impairment in obsessive compulsive disorder.

There is evidence that nonverbal memory problems in obsessive compulsive disorder (OCD) are mediated by impaired strategic processing. Although many studies have found verbal memory to be normal in OCD, these studies did not use tests designed to stress organizational strategies. This study examined verbal and nonverbal memory performance in 33 OCD patients and 30 normal control participants with the Rey-Osterrieth Complex Figure Test and the California Verbal Learning Test. OCD patients were impaired on verbal and nonverbal measures of organizational strategy and free recall. Multiple regression modeling indicated that free recall problems in OCD were mediated by impaired organizational strategies used during learning trials. Therefore, verbal and nonverbal episodic memory deficits in OCD are affected by impaired strategic processing. Results are consistent with neurobiological models proposing frontal-striatal system dysfunction in OCD.