A pilot study exploring the association of morphological changes with 5-HTTLPR polymorphism in OCD patients.

BACKGROUND: Clinical and pharmacological studies of obsessive-compulsive disorder (OCD) have suggested that the serotonergic systems are involved in the pathogenesis, while structural imaging studies have found some neuroanatomical abnormalities in OCD patients. In the etiopathogenesis of OCD, few studies have performed concurrent assessment of genetic and neuroanatomical variables. METHODS: We carried out a two-way ANOVA between a variable number of tandem repeat polymorphisms (5-HTTLPR) in the serotonin transporter gene and gray matter (GM) volumes in 40 OCD patients and 40 healthy controls (HCs). RESULTS: We found that relative to the HCs, the OCD patients showed significant decreased GM volume in the right hippocampus, and increased GM volume in the left precentral gyrus. 5-HTTLPR polymorphism in OCD patients had a statistical tendency of stronger effects on the right frontal pole than those in HCs. CONCLUSIONS: Our results showed that the neuroanatomical changes of specific GM regions could be endophenotypes of 5-HTTLPR polymorphism in OCD.

Biological heterogeneity of obsessive-compulsive disorder: A voxel-based morphometric study based on dimensional assessment.

AIM: Although many neuroimaging studies of obsessive-compulsive disorder (OCD) have reported broad abnormalities in gray matter (GM), their results remain inconsistent. One reason for this inconsistency could be the heterogeneity of OCD. In the present study, we aimed to classify alterations in brain anatomy by OCD subtype. METHODS: Magnetic resonance imaging examinations of 37 OCD patients and 37 matched healthy controls were conducted using a 3.0-Tesla scanner. In the voxel-based morphometric procedure, preprocessed GM structural images were used to compare the two groups, and multiple regression analysis was used to investigate the correlation between regional GM volume in OCD patients and the OCD symptom dimension type assessed by using the Dimensional Yale-Brown Obsessive-Compulsive Scale. RESULTS: We found significant reductions in GM volume in broad areas of the left prefrontal, right orbitofrontal, right parietal, right temporal, and right posterior cingulate cortex in the OCD patients compared to healthy controls. In addition, we found specific negative correlations between symptomatic dimension scores and regional GM volumes, mainly as decreased right cerebellum in 'aggression/checking' and decreased right insula in 'contamination/washing'. CONCLUSION: The pathophysiology of OCD may involve widely distributed neural systems. Moreover, there are distinct correlations among symptomatic dimensions and structural abnormalities.

Neurobiological model of obsessive-compulsive disorder: evidence from recent neuropsychological and neuroimaging findings.

Obsessive-compulsive disorder (OCD) was previously considered refractory to most types of therapeutic intervention. There is now, however, ample evidence that selective serotonin reuptake inhibitors and behavior therapy are highly effective methods for treatment of OCD. Furthermore, recent neurobiological studies of OCD have found a close correlation between clinical symptoms, cognitive function, and brain function. A large number of previous neuroimaging studies using positron emission tomography, single-photon emission computed tomography or functional magnetic resonance imaging (fMRI) have identified abnormally high activities throughout the frontal cortex and subcortical structures in patients with OCD. Most studies reported excessive activation of these areas during symptom provocation. Furthermore, these hyperactivities were decreased after successful treatment using either selective serotonin reuptake inhibitors or behavioral therapy. Based on these findings, an orbitofronto-striatal model has been postulated as an abnormal neural circuit that mediates symptomatic expression of OCD. On the other hand, previous neuropsychological studies of OCD have reported cognitive dysfunction in executive function, attention, nonverbal memory, and visuospatial skills. Moreover, recent fMRI studies have revealed a correlation between neuropsychological dysfunction and clinical symptoms in OCD by using neuropsychological tasks during fMRI. The evidence from fMRI studies suggests that broader regions, including dorsolateral prefrontal and posterior regions, might be involved in the pathophysiology of OCD. Further, we should consider that OCD is heterogeneous and might have several different neural systems related to clinical factors, such as symptom dimensions. This review outlines recent neuropsychological and neuroimaging studies of OCD. We will also describe several neurobiological models that have been developed recently. Advanced findings in these fields will update the conventional biological model of OCD.

Clinical characteristics of hoarding disorder in Japanese patients.

Previous studies have reported clinical characteristics of hoarding disorder (HD), such as early onset, a chronic course, familiality, high unmarried rate, and high rates of comorbidities. However, clinical research targeting Japanese HD patients has been very limited. As a result, there is a low recognition of HD in Japan, leading to insufficient evaluation and treatment of Japanese HD patients. The aim of the current study was to delineate the clinical characteristics of Japanese HD patients. Thirty HD patients, 20 obsessive-compulsive disorder (OCD) patients, and 21 normal controls (NC) were targeted in this study. The HD group had a tendency toward higher familiality, earlier onset, and longer disease duration compared to the OCD group. In addition, the HD group showed a significantly higher unmarried rate than the NC group. The top two comorbidities in the HD group were major depressive disorder (56.7%) and attention-deficit/hyperactivity disorder (26.7%). The HD group had significantly higher scores on hoarding rating scales and lower scores on the Global Assessment of Functioning Scale than the other two groups. The current study showed a clinical trend in Japanese HD patients similar to previous studies in various countries, suggesting that HD may be a universal disease with consistent clinical symptoms.

Identification of okadaic acid binding protein 2 in reconstituted sponge cell clusters from Halichondria okadai and its contribution to the detoxification of okadaic acid.

Okadaic acid (OA) and OA binding protein 2 (OABP2) were previously isolated from the marine sponge Halichondria okadai. Because the amino acid sequence of OABP2 is completely different from that of protein phosphatase 2A, a well-known target of OA, we have been investigating the production and function of OABP2. In the present study, we hypothesized that OABP2 plays a role in the detoxification of OA in H. okadai and that the OA concentrations are in proportional to the OABP2 concentrations in the sponge specimens. Based on the OA concentrations and the OABP2 concentrations in the sponge specimens collected in various places and in different seasons, however, we could not determine a positive correlation between OA and OABP2. We then attempted to determine distribution of OA and OABP2 in the sponge specimen. When the mixture of dissociated sponge cells and symbiotic species were separated with various pore-sized nylon meshes, most of the OA and OABP2 was detected from the same 0-10 µm fraction. Next, when sponge cell clusters were prepared from a mixture of dissociated sponge cells and symbiotic species in the presence of penicillin and streptomycin, we identified the 18S rDNA of H. okadai and the gene of OABP2 in the analysis of genomic DNA but could not detect OA by LC-MS/MS. We thus concluded that the sponge cells express OABP2, and that OA was not apparently present in the sponge cells but could be colocalized with OABP2 in the sponge cells at a concentration less than the limit of detection.

Refractory seborrheic dermatitis of the head in a patient with malignant lymphoma.

Seborrheic dermatitis is an inflammatory eruption that tends to distribute on the sebaceous areas of the body and is rarely described as a paraneoplasia. Here we report a case with a responsive seborrheic dermatitis-like eruption of the head which resulted in generalized erythroderma. Intensive examinations detected concurrent malignant lymphoma.

Differential neural network of checking versus washing symptoms in obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is clinically heterogeneous. The aim of this study was to investigate differential neural responses to a symptom provocation task in drug-free patients who have predominantly aggression/checking symptoms (Checkers) and patients with contamination/washing symptoms (Washers). We compared the Checkers (n=10) and the Washers (n=12) separately to normal controls during the symptom provocation tasks using fMRI (functional magnetic resonance imaging). Moreover, we performed correlative analysis in each OCD group between brain activation and symptom severity. The Checkers showed hypoactivation in the left caudate and left anterior cingulate cortex (ACC) compared to the normal controls and a positive correlation between activated brain areas and symptom severity in the left ACC. The Washers showed hyperactivation in several bilateral cortico-cerebellar regions and a positive correlation between symptom severity and the bilateral fronto-temporal gyrus. We suggest that the caudate and ACC are associated with checking rituals and that large cortical brain regions are related to washing rituals.