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.

Neural substrates of anorexia nervosa: a behavioral challenge study with positron emission tomography.

OBJECTIVE: To delineate functional brain abnormalities associated with anorexia nervosa (AN). STUDY DESIGN: Positron emission tomographic measurements of regional cerebral blood flow (rCBF) were performed on 8 female patients with AN and 8 healthy female control subjects during exposure to 3 types of stimuli: high-calorie foods, low-calorie foods, and non-food items. Heart rate and internal state analog scale scores were also obtained. Stereotactic transformation and statistical parametric mapping techniques were used to analyze imaging data. RESULTS: During the high-calorie condition, control subjects reported a significant desire to eat, whereas subjects with AN reported elevated anxiety and exhibited increases in heart rate. Patients with AN had elevated bilateral medial temporal lobe rCBF compared with control subjects. Planned comparisons for group-by-condition interactions demonstrated greater activation within left occipital cortex and right temporo-occipital cortex for the high-calorie versus low-calorie contrast in patients with AN compared with control subjects. CONCLUSIONS: Our finding of elevated rCBF within bilateral medial temporal lobes is similar to published results in patients with psychotic disorders and may be related to the body image distortion common to AN. The high-calorie food phobia exhibited by patients with AN appears to be associated with exaggerated responses in visual association cortex, as has been previously observed in studies of specific phobias.

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.

Phenomenological differences appearing with repetitive behaviours in obsessive-compulsive disorder and Gilles de la Tourette's syndrome.

BACKGROUND: Obsessive-compulsive disorder (OCD) is heterogeneous, with some forms related to Gilles de la Tourette's syndrome (GTS). This is a phenomenological study designed to investigate the nature of these possible OCD subtypes and the relationship between OCD and GTS. METHOD: We evaluated 20 adult outpatients with OCD, 21 with GTS, and 20 with OCD plus GTS using a semi-structured interview designed to assess cognitive, sensory and autonomic phenomena preceding repetitive behaviours. RESULTS: More cognitions and autonomic anxiety and fewer sensory phenomena were reported in OCD than in GTS. Like the GTS group, the OCD plus GTS group reported more sensory phenomena and fewer cognitions than the OCD group. CONCLUSIONS: The presence or absence of cognitions, sensory phenomena, and autonomic anxiety distinguishes repetitive behaviours in patients with OCD from those with OCD plus GTS, and GTS. These subjective experiences may be useful in subtyping OCD and may represent valid predictors of prognosis and treatment response.

Current controversies and future directions in basal ganglia research. Integrating basic neuroscience and clinical investigation.

This article discusses current controversies and future directions in basal ganglia research, detailing behavioral aspects, anatomic models, neurochemistry, pharmacology, and diagnostic methods as well as surgical techniques. A neuroethologic perspective is highlighted. Furthermore, the relevant literature pertaining to contemporary molecular approaches such as brain microinjections of embryonic or genetically modified cells, for therapeutic purposes and the use of transgenic and knockout animals.

Obsessive-compulsive spectrum disorders in patients with obsessive-compulsive disorder and Tourette's syndrome

Introduction: Obsessive-Compulsive Spectrum Disorders include Obsessive-Compulsive Disorder (OCD), Tourette's Disorder (TS), Body Dysmorphic Disorder (BDD) and Trichotillomania (TTM), which, supposedly, share common psychopathological, physiopathological and genetic aspects. To date, the relation of OCD and TS is the most established. Recent studies suggest that patients with OCD and TS have a better response to serotonin reuptake inhibitors (SRI) plus neuroleptics than to SRI alone. Thus, the detection of patients with OCD and tics is important, once it can point to a different psychopharmacological approach. Similarly, the recognition of other psychiatric disorders associated to OCD could indicate important factors in treatment response. This study compares psychiatric comorbidity in patients with OCD and OCD plus TS, with the following hypotheses: 1) The group with both TS and OCD would be at significant risk for greater severity and frequency of associated disorders; 2) TTM would be more frequent in the OCD plus TS group, whereas BDD would be more frequent in the OCD group. Method: Twenty outpatients with OCD and twenty with OCD plus TS (DSM-III-R) were evaluated by the Standar Clinical Interview for the DSM-III-R (SCID) and additional modules designed by the authors for the diagnosis of TS, Chronic Motor Tics, BDD, TTM and Attention Deficit Disorder. Results: 1) Within groups: In the OCD group, the most frequent diagnoses were:...