Brain functional connectivity during induced sadness in patients with obsessive-compulsive disorder

Background

Obsessive–compulsive disorder (OCD) is associated with a range of emotional abnormalities linked to its defining symptoms, comorbid illnesses and cognitive deficits. The aim of this preliminary study was to examine functional changes in the brain that are associated with experimentally induced sad mood in patients with OCD compared with healthy controls in a frontolimbic circuit relevant to both OCD and mood regulation.

Methods

Participants underwent a validated sad mood induction procedure during functional magnetic resonance imaging. Analyses focused on mapping changes in the functional connectivity of the subgenual anterior cingulate cortex (ACC) within and between the 2 groups in response to successfully induced sadness.

Results

We enrolled 11 patients with OCD and 10 age-, sex- and IQ-matched controls in our study. Unlike controls, patients with OCD did not demonstrate predicted increases in functional connectivity between the subgenual ACC and other frontal regions during mood induction. Instead, patients demonstrated heightened connectivity between the subgenual ACC and ventral caudate/nucleus accumbens region and the hypothalamus.

Limitations

Our study included a small, partially medicated patient cohort that precluded our ability to investigate sex or drug effects, evaluate behavioural differences between the groups and perform a whole-brain analysis.

Conclusion

The ventral striatum and ventral frontal cortex were distinctly and differentially modulated in their connectivity with the subgenual ACC during the experience of sad mood in patients with OCD. These results suggest that, in patients with OCD, induced sadness appears to have provoked a primary subcortical component of the hypothesized “OCD circuit,” which may offer insights into why OCD symptoms tend to develop and worsen during disturbed emotional states.     

Vulnerability of an epileptic case to psychosis: Sodium valproate with lamotrigine, forced normalization, postictal psychosis or all?

Patients with epilepsy can be considered to be at high risk for developing psychotic disorders. Furthermore, there is association between seizure freedom or the disappearance of the interictal epileptiform events from the EEG record and the occurrence of psychotic symptoms. Also, several newer antiepileptic drugs have been reported to induce psychotic symptoms. We present a patient with epilepsy who developed psychotic symptoms under the treatment of valproic acid (VPA) and lamotrigine (LTG) combination. The mechanism underlying the association between LTG, seizure control and development of psychosis are discussed in the light of the literature.     

Neuroanatomical abnormalities in schizophrenia: a multimodal voxelwise meta-analysis and meta-regression analysis

Despite an increasing number of published voxel based morphometry studies of schizophrenia, there has been no adequate attempt to examine gray (GM) and white matter (WM) abnormalities and the heterogeneity of published findings. In the current article, we used a coordinate based meta-analysis technique to simultaneously examine GM and WM abnormalities in schizophrenia and to assess the effects of gender, chronicity, negative symptoms and other clinical variables. 79 studies meeting our inclusion criteria were included in the meta-analysis. Schizophrenia was associated with GM reductions in the bilateral insula/inferior frontal cortex, superior temporal gyrus, anterior cingulate gyrus/medial frontal cortex, thalamus and left amygdala. In WM analyses of volumetric and diffusion-weighted images, schizophrenia was associated with decreased FA and/or WM in interhemispheric fibers, anterior thalamic radiation, inferior longitudinal fasciculi, inferior frontal occipital fasciculi, cingulum and fornix. Male gender, chronic illness and negative symptoms were associated with more severe GM abnormalities and illness chronicity was associated with more severe WM deficits. The meta-analyses revealed overlapping GM and WM structural findings in schizophrenia, characterized by bilateral anterior cortical, limbic and subcortical GM abnormalities, and WM changes in regions including tracts that connect these structures within and between hemispheres. However, the available findings are biased towards characteristics of schizophrenia samples with poor prognosis.     

Theory of mind impairment: a distinct trait‐marker for schizophrenia spectrum disorders and bipolar disorder?

Objective: The aim of this study was to critically review the literature in order to determine if Theory of Mind (ToM) impairment can be considered a trait‐marker for schizophrenia spectrum disorders and bipolar disorder (BD). Method: After a thorough literature search, we reviewed the empirical studies investigating ToM impairments in remitted schizophrenia patients, first episode patients, subjects at high‐risk (HR) for psychosis and first‐degree relatives of schizophrenia patients. Studies investigating ToM impairment in other schizophrenia spectrum conditions, affective psychosis and BD were also reviewed. Results: ToM abnormalities exist at onset and continue throughout the course of schizophrenia, persist into remission, and while less severe, are apparent in HR populations. Mentalizing impairments are also observed in other forms of psychotic illness and BD. Conclusion: Mentalizing impairment in schizophrenia spectrum disorders and BD might reflect underlying general cognitive deficits and residual symptom expression, rather than representing a specific trait‐marker.     

Analysis of high-voltage electrical spinal cord injury using diffusion tensor imaging

The aim of this study was to investigate spinal cord injury (SCI) on the basis of diffusion tensor imaging (DTI) in patients with high-voltage electrical injury. We recruited eight high-voltage electrical injury patients and eight healthy subjects matched for age and sex. DTI and central motor conduction time were acquired in both the patient and control groups. We obtained DTI indices according to the spinal cord levels (from C2 to C7) and cross-section locations (anterior, lateral, and posterior). Fractional anisotrophy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were compared between the two groups; additionally, they were compared in relation to spinal cord level and cross-section location. In the patient group relative to the control group, the FA value decreased and the MD and RD values increased in all of the regions of interest (ROI) with statistical significance (p < 0.05). In the patient group, particularly in the ROIs of the anterior spinal cord compared with the lateral and posterior spinal cords, the FA value decreased with statistical significance (p < 0.05). The DTI indices did not differ by level. DTI revealed the change of diffusion in the spinal cords of patients with high-voltage electrical injury, and corroborated the pathophysiology, myelinopathy and typical anterior spinal cord location of high-voltage electrical SCI already reported in the literature.     

Microstructural changes in the hippocampus and posterior cingulate in mild cognitive impairment and Alzheimer’s disease: a diffusion tensor imaging study

Diffusion tensor imaging (DTI) is a sensitive MRI technique in the detection of white matter degeneration. We sought to demonstrate microstructural changes in normal controls, patients with amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD) and to determine which DTI parameters could be a reliable tool for the early diagnosis of AD. In total, 90 participants (35 normal, 20 aMCI, 35 AD) were recruited. We included early AD patients with clinical dementia rating scores of 0.5 and 1. The fractional anisotropy and mean diffusivity values, DTI parameter, were measured with the regions of interest method in the bilateral hippocampal body and posterior cingulate. Clinical history, neurological examination, and neuropsychological assessments were conducted. The DTI parameters in the bilateral hippocampus and posterior cingulate in aMCI and AD were different from those in normal controls. No difference was found in DTI parameters of the posterior cingulate between aMCI and AD. However, hippocampal DTI parameters were different between aMCI and AD. Cognitive summary measures were significantly correlated with DTI parameters, especially FA values in the hippocampus. The DTI analysis technique demonstrated significant microstructural alterations in the hippocampus and posterior cingulate already in prodromal stage of AD. DTI parameters in the hippocampus may be a more sensitive method to determine microstructural changes in early AD states and more correlated with cognition than DTI parameters in the posterior cingulate.     

Preparation and characterization of Antheraea assama silk fibroin based novel non‐woven scaffold for tissue engineering applications

The quest for novel materials as scaffolds with suitable micro‐architecture for supporting tissue neogenesis in tissue engineering and regenerative medicine (TERM) is continuing. In this paper we report an Antheraea assama silk‐based non‐woven fibroin scaffold for applications in TERM. The novel three‐dimensional scaffold is highly interconnected and porous, with a pore size of 150 µm, porosity of 90% and water uptake capacity of 85%. FTIR revealed a typical β‐sheet structure of fibroin. The scaffold has thermal and mechanical properties superior to those of Bombyx mori, as revealed by DSC, TGA and tensile tests. The scaffold exhibited satisfactory blood compatibility, as determined by thrombogenicity, haemolysis, platelet/leukocyte count, platelet adhesion and protein adsorption studies. The scaffold was found to be cytocompatible with human cell lines A549, KB, HepG2 and HeLa for a period of up to 4 weeks. SEM analysis revealed excellent attachment, spreading and migration of cells in the scaffold. MTT assay was performed to estimate the viability and growth of cells in the matrix. Quantification of collagen in cell–scaffold constructs was done by picro‐Sirius red assay. Ex ovo chorioallantoic membrane assay and nitric oxide estimations in spent culture medium showed the scaffold's ability to promote angiogenesis. Finally, the biodegradability of the scaffold was determined by the weight loss observed upon treatment with trypsin over a period of 4 weeks. The results reveal that the fibroin from A. assama is a promising candidate as a biocompatible, biomimetic and biodegradable biomaterial of natural origin for applications in TERM. Copyright © 2009 John Wiley & Sons, Ltd.     

Expression of B7 molecules in the eye during experimental autoimmune anterior uveitis (EAAU)

PURPOSE: We have reported that CTLA4-Fc, a fusion protein that binds B7, prevents the induction of EAAU and reduces the severity of disease in Lewis rats. Since B7.1 and B7.2 have distinctive roles in other autoimmune diseases, we investigated their roles in the development of EAAU. METHODS: Lewis rats were immunized with melanin associated antigen (MAA). Eyes were collected at different stages of EAAU and the expression of B7 on iris and ciliary body (ICB) cell suspensions determined by flow cytometry analysis. The incidence of EAAU after treatment with anti B7, and the requirement of B7.1 and B7.2 for proliferation and cytokine production of lymphoid cells to MAA were also studied. RESULTS: B7.2 is up-regulated in resident ICB cells or bone-marrow derived cells which have infiltrated the ICB by day 10 and remains elevated during the acute phase of disease. B7.1 is expressed later during the acute phase. Both B7.1 and B7.2 are down-regulated during remission, with low levels of B7.2 and no detectable B7.1. The incidence of EAAU was reduced by anti-B7.2 treatment and completely inhibited by a combination of both B7.1 and B7.2 antibodies. Neither anti-B7.1 nor anti-B7.2 alone affected proliferation or cytokine production. However, administration of both anti-B7.1 and B7.2 completely inhibited proliferation as well as IL-2 and TNF-alpha production. CONCLUSIONS: B7.1 and B7.2 are expressed in the eye at different times during EAAU. Both B7 molecules are required for the induction of EAAU, although they probably have different roles.     

A mannosyltransferase gene at 11q23 is disrupted by a translocation breakpoint that co-segregates with bipolar affective disorder in a small family

Bipolar affective disorder (BPAD) is a complex neuropsychiatric disease characterized by extreme mood swings. Genetic influences affect the disease susceptibility substantially, yet the underlying mechanisms are unknown. We previously described a pedigree in which all five individuals with BPAD and one individual with recurrent major depression were carriers of a reciprocal chromosomal translocation t(9;11)(p24;q23). Gene content analyses of the breakpoint junctions revealed disruption of a gene (DIBD1) at 11q23, a genomic region that has also been implicated in schizophrenia and Tourette syndrome. DIBD1 is predicted to encode a mannosyltransferase similar to Saccaromyces cerevisiae Alg9p of the protein N-glycosylation pathway. The inborn errors of protein N-glycosylation cause congenital disorders of glycosylation in humans. DIBD1 shows uniform expression in the tested subregions of the brain by Northern analysis. Sequence analysis revealed four intra-genic single nucleotide polymorphisms. The valine residue at V289I was conserved in other eukaryotic species, whereas its frequency was approximately 65% in humans. We performed linkage and linkage disequilibrium analyses in two NIMH bipolar pedigree series using four tightly linked simple tandem repeat polymorphisms (STRPs) and the V289I. These analyses overall failed to support a role for DIBD1 in disease susceptibility. The most-significant finding was a lod score of 1.18 (P=0.0098), obtained by an intronic STRP D11S5025, in the subset of 22 multiplex pedigrees. In conclusion, we found that a mannosyltransferase gene at 11q23 is disrupted by a translocation breakpoint co-segregating with BPAD in a family. However, its role in the disease susceptibility remains unconfirmed. Electronic Publication