Widespread abnormality of the γ-aminobutyric acid-ergic system in Tourette syndrome.

Dysfunction of the γ-aminobutyric acid-ergic system in Tourette syndrome may conceivably underlie the symptoms of motor disinhibition presenting as tics and psychiatric manifestations, such as attention deficit hyperactivity disorder and obsessive-compulsive disorder. The purpose of this study was to identify a possible dysfunction of the γ-aminobutyric acid-ergic system in Tourette patients, especially involving the basal ganglia-thalamo-cortical circuits and the cerebellum. We studied 11 patients with Tourette syndrome and 11 healthy controls. Positron emission tomography procedure: after injection of 20 mCi of [(11)C]flumazenil, dynamic emission images of the brain were acquired. Structural magnetic resonance imaging scans were obtained to provide an anatomical framework for the positron emission tomography data analysis. Images of binding potential were created using the two-step version of the simplified reference tissue model. The binding potential images then were spatially normalized, smoothed and compared between groups using statistical parametric mapping. We found decreased binding of GABA(A) receptors in Tourette patients bilaterally in the ventral striatum, globus pallidus, thalamus, amygdala and right insula. In addition, the GABA(A) receptor binding was increased in the bilateral substantia nigra, left periaqueductal grey, right posterior cingulate cortex and bilateral cerebellum. These results are consistent with the longstanding hypothesis that circuits involving the basal ganglia and thalamus are disinhibited in Tourette syndrome patients. In addition, the abnormalities in GABA(A) receptor binding in the insula and cerebellum appear particularly noteworthy based upon recent evidence implicating these structures in the generation of tics.

Obsessive-compulsive disorder symptom dimensions show specific relationships to psychiatric comorbidity.

The goals of this study were to examine relationships among symptom categories in obsessive-compulsive disorder (OCD), to establish OCD symptom dimensions by factor- and cluster-analytic analyses, and to explore associations between OCD symptom dimensions and comorbid neuropsychiatric conditions. A total of 317 OCD participants underwent a systematic diagnostic interview using the Structured Clinical Interview for DSM-IV. OCD symptoms assessed by the Yale-Brown Obsessive-Compulsive Scale Symptom Checklist (N=169) and by the Thoughts and Behaviors Inventory (N=275) were subjected to factor and cluster analyses. An identical four-factor solution emerged in two different data sets from overlapping samples, in agreement with most smaller factor-analytic studies employing the YBOCS checklist alone. The cluster analysis confirmed the four-factor solution and provided additional information on the similarity among OCD symptom categories at five different levels. OCD symptom dimensions showed specific relationships to comorbid psychiatric disorders: Factor I (aggressive, sexual, religious and somatic obsessions, and checking compulsions) was broadly associated with comorbid anxiety disorders and depression; Factor II (obsessions of symmetry, and repeating, counting and ordering/arranging compulsions) with bipolar disorders and panic disorder/agoraphobia; and Factor III (contamination obsessions and cleaning compulsions) with eating disorders. Factors I and II were associated with early onset OCD. This study encourages the use of cluster analyses as a supplementary method to factor analyses to establish psychiatric symptom dimensions. The frequent co-occurrence of OCD with other psychiatric disorders and the relatively specific association patterns between OCD symptom dimensions and comorbid disorders support the importance of OCD subtyping for treatment, genetic, and other research studies of this heterogeneous disorder.

Factor analysis of obsessive-compulsive disorder YBOCS-SC symptoms and association with 5-HTTLPR SERT polymorphism.

Symptoms defining obsessive-compulsive disorder (OCD) are diverse. Factor analyses of OCD symptoms have been used to evaluate obsessive-compulsive phenotypes that are thought to be more homogenous than the macro phenotype. There is evidence that three factors (symmetry/ordering, obsessions/checking, and hoarding) are familial and preliminary evidence that repetitive rituals are associated with a functional polymorphism in the promotor region of the serotonin transporter gene (5-HTTLPR). The goal of this study was to examine relationships between OCD symptom dimensions and 5-HTTLPR. We genotyped 153 subjects who met DSM-IV criteria for OCD. We used the Yale-Brown obsessive-compulsive scale symptom checklist (YBOCS-SC) to assess OCD symptoms. Using principle components analysis, we derived four factors from the 13 symptom categories of the YBOCS-SC in this patient sample, which replicated previous factor analyses of this scale. The frequencies of the S allele and the SS genotype were associated with the second factor including obsessions regarding symmetry and compulsions involving repeating, counting, and ordering/arranging. This study may contribute to understanding of molecular genetic features underlying the appearance of symptom clusters in OCD.

Diagnostic interview assessed neuropsychiatric disorder comorbidity in 334 individuals with obsessive-compulsive disorder.

Is obsessive-compulsive disorder (OCD) a discrete disorder? Three hundred thirty-four individuals with OCD were interviewed using the Structured Clinical Interview for DSM (SCID). Results demonstrate that OCD is highly comorbid with other neuropsychiatric disorders, with 92% of OCD study participants receiving one or more additional Axis I DSM diagnoses. Among these additional diagnoses, lifetime mood disorders (81%) and anxiety disorders (53%) were the most prevalent. With the exception of substance-related disorders and specific phobias, all disorders assessed were found in considerably higher frequency than in the general population, indicating that OCD is associated with highly complex comorbidity. These data have implications for genetic studies of OCD and disorders related to OCD, as well as for specific psychotherapeutic and psychopharmacologic interventions.