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Biomedical subjects

E C Miguel

Publications and source records attributed to E C Miguel.

At least 19 recordsLinked to original sources
PubMed2006

The Dimensional Yale-Brown Obsessive-Compulsive Scale (DY-BOCS): an instrument for assessing obsessive-compulsive symptom dimensions.

Obsessive-compulsive disorder (OCD) encompasses a broad range of symptoms representing multiple domains. This complex phenotype can be summarized using a few consistent and temporally stable symptom dimensions. The objective of this study was to assess the psychometric properties of the Dimensional Yale-Brown Obsessive-Compulsive Scale (DY-BOCS). This scale measures the presence and severity of obsessive-compulsive (OC) symptoms within six distinct dimensions that combine thematically related obsessions and compulsions. The DY-BOCS includes portions to be used as a self-report instrument and portions to be used by expert raters, including global ratings of OC symptom severity and overall impairment. We assessed 137 patients with a Diagnostic and Statistical Manual-IV diagnosis of OCD, aged 6-69 years, from sites in the USA, Canada and Brazil. Estimates of the reliability and validity of both the expert and self-report versions of the DY-BOCS were calculated and stratified according to age (pediatric vs. adult subjects). The internal consistency of each of the six symptom dimensions and the global severity score were excellent. The inter-rater agreement was also excellent for all component scores. Self-report and expert ratings were highly intercorrelated. The global DY-BOCS score was highly correlated with the total Yale-Brown Obsessive-Compulsive Scale score (Pearson r = 0.82, P<0.0001). Severity scores for individual symptom dimensions were largely independent of one another, only modestly correlated with the global ratings, and were also differentially related to ratings of depression, anxiety and tic severity. No major differences were observed when the results were stratified by age. These results indicate that the DY-BOCS is a reliable and valid instrument for assessing multiple aspects of OCD symptom severity in natural history, neuroimaging, treatment response and genetic studies when administered by expert clinicians or their highly trained staff.

Adolescent↗
PubMed2005

Obsessive-compulsive disorder phenotypes: implications for genetic studies.

Obsessive-compulsive disorder (OCD) clinical presentation is remarkably diverse, and can vary both within and across patients over time. This variability in the phenotypic expression has led to the hypothesis that OCD is a heterogeneous disorder and that this heterogeneity obscures the findings of clinical, natural history and treatment response studies and complicates the search for vulnerability genes. A complete understanding of what comprises OCD and the underlying etiological mechanisms will require a dramatic change in how the disorder is conceptualized. In this review, several different approaches that may represent the first steps in this reconceptualization are discussed. These approaches include (1) narrowing the phenotype to identify categorically defined more homogeneous and mutually exclusive subtypes of OCD, (2) considering OC symptom dimensions as quantitative components of the more complex OCD phenotype and (3) broadening the phenotype to include other etiologically related conditions. A combined dimensional approach within distinctive subgroups is proposed as probably the most effective in helping to identify the heritable components of OCD. By identifying heritable components of OCD, it should be possible to find genes for these separate components. The review continues with the illustration of the possible role of some epigenetic risk and protective factors in the OCD presentation and the relevance of examining associated traits and/or endophenotypes to enhance our ability to understand the genetic basis of OCD. To conclude, we discuss the variability in treatment outcome and the significance of the development of specific pharmacological and/or behavioral based therapies tailored to each of these phenotypes.

Epigenesis, Genetic↗
PubMed2004

Association analysis of the catechol-o-methyltransferase (COMT), serotonin transporter (5-HTT) and serotonin 2A receptor (5HT2A) gene polymorphisms with obsessive-compulsive disorder.

Family and twin studies have supported a strong genetic factor in the etiology of obsessive-compulsive disorder (OCD), although the precise mechanism of inheritance is unclear. Clinical and pharmacological studies have implicated the serotonergic and dopaminergic systems in disease pathogenesis. In this cross-sectional study, we have examined the allelic and genotypic frequencies of a Val-158-Met substitution in the COMT gene, a 44-base pair (bp) length variation in the regulatory region of the serotonin transporter gene (5-HTTLPR) and the T102C and C516T variants in the serotonin receptor type 2A (5HT2A) gene in 79 OCD patients and 202 control subjects. There were no observed differences in the frequencies of allele and genotype between patients and control groups for the COMT, the 5HTTLPR and the T102C 5HT2A gene polymorphisms. In contrast, a statistically significant difference between OCD patients and controls was observed on the genotypic distribution (chi(2) = 16.7, 2df, P = 0.0002) and on the allelic frequencies (chi(2) = 15.8, 1df, P = 0.00007) for the C516T 5HT2A gene polymorphism. The results suggest that the C516T variant of the 5HT2A gene may be one of the genetic risk factors for OCD in our sample. However, further studies using larger samples and family based methods are recommended to confirm these findings.

Adult↗
PubMed2001

Antibodies against neural, nuclear, cytoskeletal, and streptococcal epitopes in children and adults with Tourette's syndrome, Sydenham's chorea, and autoimmune disorders.

BACKGROUND: Some cases of Tourette's syndrome (TS) are hypothesized to be caused by autoantibodies that develop in response to a preceding group A beta hemolytic streptococcal infection. METHODS: To test this hypothesis, we looked for the presence ot total and IgG antibodies against neural, nuclear, cytoskeletal and streptococcal epitopes using indirect immunofluorescent assays and Western blot techniques in three patient groups: TS (n = 81), SC (n = 27), and a group of autoimmune disorders (n = 52) and in normal controls (n = 67). Subjects were ranked after titrations of autoantibodies from 0 to 227 according to their level of immunoreactivity. RESULTS: TS patients had a significantly higher mean rank for total antineural and antinuclear antibodies, as well as antistreptolysin O titers. However, among children and adolescents, only the total antinuclear antibodies were increased in TS patients compared to age matched controls. Compared to SC patients, TS patients had a significantly lower mean rank for total and IgG class antineural antibodies, significantly lower IgG class anticytoskeletal antibodies, and a significantly higher rank for total antinuclear antibodies. Compared to a mixed group of autoimmune disorders, the TS patients had a significantly lower mean rank for total and IgG class antineural antibodies, total and IgG class antinuclear antibodies, IgG class anticytoskeletal antibodies, and a significantly higher rank for antistreptococcal antibodies. CONCLUSIONS: TS patients had significantly higher levels of total antineural and antinuclear antibodies than did controls. Their relation to IgG class antineural and antinuclear antibodies, markers for prior streptococcal infection, and other clinical characteristics, especially chronological age, was equivocal.

Adolescent↗
PubMed2001

OCD and transvestism: is there a relationship?

OBJECTIVE: There have been reports of obsessive-compulsive disorder (OCD) patients with comorbid paraphilias. In this paper, two cases of comorbidity between OCD and transvestism are reported with the aim of discussing possible explanations for this association. METHOD: Longitudinal case studies of two patients with OCD and tranvestism according to the DSM-IV were assessed using semi-structured interviews. RESULTS: Both patients presented with OCD and comorbid transvestism with different clinical features and treatment response. The case whose cross-dressing was more egodystonic responded better to treatment. CONCLUSION: It is possible that some cases of transvestism are OCD-related while others are more related to a gender identity disorder. A dimensional approach focusing on common phenomenological and neurobiological substrates is suggested as particularly useful for clinical management and future research of both disorders.

Adult↗
PubMed2001

Regional cerebral blood flow abnormalities in early-onset obsessive-compulsive disorder: an exploratory SPECT study.

OBJECTIVE: Recent epidemiological and clinical data suggest that obsessive-compulsive disorder (OCD) may be subtyped according the age of onset of obsessive-compulsive symptoms. The regional cerebral blood flow (rCBF) single photon emission computed tomography (SPECT) technique was used to investigate whether the pathophysiology of OCD differs between early- and late-onset OCD subjects. METHOD: Resting rCBF was measured in 13 early-onset (<10 years) and 13 late-onset (>12 years) adult OCD subjects and in 22 healthy controls. Voxel-based rCBF comparisons were performed with statistical parametric mapping. RESULTS: Early-onset OCD cases showed decreased rCBF in the right thalamus, left anterior cingulate cortex, and bilateral inferior prefrontal cortex relative to late-onset subjects (p < .0005, uncorrected for multiple comparisons). Relative to controls, early-onset cases had decreased left anterior cingulate and right orbitofrontal rCBF, and increased rCBF in the right cerebellum, whereas late-onset subjects showed reduced right orbitofrontal rCBF and increased rCBF in the left precuneus. In early-onset subjects only, severity of obsessive-compulsive symptoms correlated positively with left orbitofrontal rCBF. CONCLUSIONS: rCBF differences in frontal-subcortical circuits between early-onset and late-onset OCD subjects were found, both in location and direction of changes. These results provide preliminary evidence that brain mechanisms in OCD may differ depending on the age at which symptoms are first expressed.

Adolescent↗
PubMed2001

Adults with early-onset obsessive-compulsive disorder.

OBJECTIVE: Obsessive-compulsive disorder (OCD) is a clinically heterogeneous disorder with a bimodal age at onset and range of treatment outcomes. This study attempted to ascertain the importance of the age at OCD symptom onset for a better phenotypic precision. Therefore, the authors compared adult OCD patients with an early symptom onset to OCD patients with a later symptom onset. METHOD: Forty-two adult outpatients with OCD were evaluated with semistructured interviews: 21 with symptom onset before the age of 10 (early-onset group) and 21 with symptom onset after the age of 17 (late-onset group). RESULTS: Early onset was associated with higher scores on the Yale-Brown Obsessive Compulsive Scale, higher frequencies of tic-like compulsions, higher frequency of sensory phenomena, and a higher rate of comorbid tic disorders. The early-onset group also responded less well to treatment with clomipramine and selective serotonin reuptake inhibitors. CONCLUSIONS: The results indicate that age at onset may be an important factor in subtyping OCD and that the phenotypic differences found were not restricted to childhood.

Adolescent↗
PubMed2001

[Gilles de la Tourette syndrome: a clinical study on 58 cases].

Gilles de la Tourette's syndrome (GTS) is a neuropsychiatric disorder with a childhood onset and is characterized by motor and vocal tics. Fifty-eight patients with GTS were evaluated during a period of three years. Thirty-six patients were male and twenty two female, with an age range of 7 to 51 years (mean 20.33 years). The male to female ratio was 1.6:1. The age of onset ranged from 3 to 15 years (mean 7.81 years). Seventy nine percent of the patients presented motor tics as the initial symptom of the disease. In terms of complex tics, coprolalia was present in 27.6% of the patients; copropraxia in 20.1%; palilalia in 20.1%; ecolalia in 27.6%; and ecopraxia in 27,6%. Associated manifestations, such as attention deficit, hyperactivity disorder and obsessive-compulsive disorder were present in 25.8% and 39.6%, respectively. Sensory phenomena were present in 54.8% of the patients.

Adolescent↗
PubMed2000

A voxel-based investigation of regional cerebral blood flow abnormalities in obsessive-compulsive disorder using single photon emission computed tomography (SPECT).

Several functional imaging studies have reported abnormalities of the orbitofrontal and anterior cingulate cortices, striatum and thalamus in obsessive-compulsive disorder (OCD). These studies have often been limited by small patient samples and image analysis methods that rely on region-of-interest (ROI) approaches. We have assessed resting regional cerebral blood flow with 99mTc-ECD SPECT in 26 unmedicated OCD patients and 22 healthy control subjects using the voxel-based Statistical Parametric Mapping method for data analysis. We found a significantly reduced ECD uptake in OCD patients relative to the control subjects in the right lateral orbitofrontal cortex, and in the left dorsal anterior cingulate cortex (P<0.001 two-tailed, uncorrected for multiple comparisons). There were significant positive correlations in the OCD group between the ECD uptake in the left lateral orbitofrontal cortex and ratings for obsessive-compulsive symptoms (OCS), and between the ECD uptake in the right medial orbitofrontal cortex and the ratings for both OCS and depressive symptoms. There were also unpredicted significant ECD uptake increases in the cerebellum in OCD patients, as well as a negative correlation between posterior cingulate ECD uptake and OCS severity (P<0.05, corrected for multiple testing). These results implicate specific subregions of the orbitofrontal and anterior cingulate cortices in the pathophysiology of OCD, as well as suggesting the involvement of other areas not usually included in ROI-based imaging studies. With the incorporation of voxel-based methods and the use of large patient samples, rCBF-SPECT studies may continue to provide valuable information about the functional anatomy of OCD.

Adult↗
PubMed2000

Characterization of trichotillomania. A phenomenological model with clinical relevance to obsessive-compulsive spectrum disorders.

Multiple approaches to characterization of TTM have been developed, including categoric definitions and dimensional considerations. When TTM is viewed in the context of other disorders with common comorbidities and overlapping similar phenomenologies, such as OCD, body dysmorphic disorder, skin picking, TS, and olfactory reference syndrome, clinical approaches to assessment and differential diagnosis are more complex. This article presents a general overview of TTM included as a background for a heuristic clinical framework for assessing obsessive-compulsive spectrum disorders. A comprehensive behavioral model of TTM as a template is presented in the context of a broader, phenomenologic approach to assessment of several other disorders. These additional conditions were chosen on clinical grounds because they seem to share some phenomenologic characteristics with TTM. It is hoped that combining a phenomenologic approach to the differentiation of repetitive behaviors (as has been valuable in advancing the understanding of repetitive behaviors in TS and OCD), coupled with a paradigmatic comprehensive behavioral assessment and treatment model of TTM, may foster the validation of such approaches for other putative obsessive-compulsive spectrum disorders. Also, the relative intensity and frequency ascribed to the various behavioral and phenomenologic components of the conditions depicted represent clinical impressions, with varying degrees of empiric support, and require objective validation. This approach is meant to serve as a point of departure for clinical assessment of these complex, interesting, and sometimes incompletely diagnosed and inadequately treated conditions. It is hoped that empiric validation or refutation of this conceptualization will stimulate additional research and provide clinicians with a general framework for assessing patients suffering from these difficult conditions. For more information about trichotillomania, contact The Trichotillomania Learning Center (TLC), 1215 Mission Street, Santa Cruz, CA 95060 (831-457-1004; www.trich.org).

Animals↗
PubMed2000

The psychiatric symptoms of rheumatic fever.

OBJECTIVE: This study examined the frequency and age at onset of psychiatric disorders among children with rheumatic fever, Sydenham's chorea, or both and a comparison group. METHOD: Twenty children with rheumatic fever, 22 with Sydenham's chorea, and 20 comparison children were assessed by means of a semistructured interview and rating scales for tic disorders and obsessive-compulsive disorder. RESULTS: Obsessive-compulsive symptoms were more frequent in both the Sydenham's chorea and rheumatic fever groups than in the comparison group. The Sydenham's chorea group had a higher frequency of major depressive disorder, tic disorders, and attention deficit hyperactivity disorder (ADHD) than both the comparison and rheumatic fever groups. ADHD symptoms were associated with a higher risk of developing Sydenham's chorea. CONCLUSIONS: Both the rheumatic fever and Sydenham's chorea groups were associated with a higher risk of developing neuropsychiatric disorders than the comparison group. ADHD appears to be a risk factor for Sydenham's chorea in children with rheumatic fever.

Age Factors↗
PubMed2000

[D8/17 marker: implication to neuropsychiatry].

Recent studies suggest that there is a relationship between rheumatic fever (RF) and some neuropsychiatric disorders. Thus, it has been thought that autoimmune mechanisms might be related to the etiology of these neuropsychiatric disorders. It has also been demonstrated that a B cell alloantigen associated to RF is also abnormally overexpressed in patients with such neuropsychiatric disorders. This alloantigen is recognised by a monoclonal antibody known as D8/17. The aim of this article is to introduce the recent work done about D8/17 and its possible implications to the study of neuropsychiatric disorders related or not to RF.

Antibodies, Monoclonal↗
PubMed2000

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.

Adult↗
PubMed1998

Tourette's disorder with and without obsessive-compulsive disorder in adults: are they different?

Clinical research has documented a bidirectional overlap between Tourette's disorder (TD) and obsessive-compulsive disorder (OCD) from familial-genetic, phenomenological, comorbidity, and natural history perspectives. Patients with Tourette's disorder plus obsessive-compulsive disorder (TD + OCD), a putative subtype, share features of both. The purpose of this exploratory study was to evaluate correlates of patients with TD, OCD, and TD + OCD to determine whether TD + OCD is a subtype of TD, OCD, or an additive form of both. Sixty-one subjects with TD, OCD, or TD + OCD were evaluated with the Structured Clinical Interview for DSM-III-R supplemented with additional modules. The three groups differed in the rates of bipolar disorder (p < .04), social phobia (p < .02), body dysmorphic disorder (p < .002), attention deficit hyperactivity disorder (p < .03), and substance use disorders (p < .04). These findings were accounted for by the elevated rates of the disorders in the TD + OCD group compared with the TD and OCD groups. These finding are most consistent with the hypothesis that TD + OCD is a more severe disorder than TD and OCD and may be more etiologically linked to TD than to OCD. These findings highlight the importance of assessment of the full spectrum of psychiatric comorbidity in patients with TD and OCD.

Adult↗