Cognitive Impairment in Schizophrenia and Affective Psychoses: Implications for DSM-V Criteria and Beyond

It has recently been suggested that the diagnostic criteria of schizophrenia should include specific reference to cognitive impairments characterizing the disorder. Arguments in support of this assertion contend that such inclusion would not only serve to increase the awareness of cognitive deficits in affected patients, among both clinicians and researchers alike, but also increase the “point of rarity” between schizophrenia and mood disorders. The aim of the current article is to examine this latter assertion in light of the recent opinion piece provided by Keefe and Fenton (Keefe RSE, Fenton WS. How should DSM-V criteria for schizophrenia include cognitive impairment? Schizophr Bull. 2007;33:912–920). Through literature review, we explore the issue of whether cognitive deficits do in fact differentiate the major psychoses. The overall results of this inquiry suggest that inclusion of cognitive impairment criteria in Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (DSM-V) would not provide a major advancement in discriminating schizophrenia from bipolar disorder and affective psychoses. Therefore, while cognitive impairment should be included in DSM-V, it should not dictate diagnostic specificity—at least not until more comprehensive evidence-based reviews of the current diagnostic system have been undertaken. Based on this evidence, we consider several alternatives for the DSM-V definition of cognitive impairment in schizophrenia, including (1) the inclusion of cognitive impairment as a specifier and (2) the definition of cognitive impairment as a dimension within a hybrid categorical-dimensional system. Given the state of current evidence, these possibilities appear to represent the most parsimonious approaches to the inclusion of cognitive deficits in the diagnostic criteria of schizophrenia and, potentially, of mood disorders.     

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     

Effect of caffeic acid phenethyl ester on cartilage in experimental osteoarthritis

Systemic lupus erythematosus (SLE) is characterized by the presence of various autoantibodies and the deposition of immune complex, which is cleared by Fcgamma receptors. Genotype analysis was done to investigate whether the FcgammaRIIIA-176F/V polymorphism is a risk factor for SLE in Koreans. We genotyped 145 Korean SLE patients and 75 control subjects for FcgammaRIIIA-176F/ V. After amplifying a 1.7-kb fragment containing the Fcgamma/RIIIA-176F/V polymorphic site using two FcgammaRIIIA gene-specific primers, we performed a nested polymerase chain reaction (PCR) for allele-specific genotyping at position 559 in FcgammaRIIIA. FcgammaRIIIA genotype or allele distribution was not significantly different between lupus patients and controls, and also between lupus nephritis patients and healthy controls. Neither creatinine clearance, 24 h urine proteinuria, number of American College of Rheumatology (ACR) criteria, nor the Systemic Lupus International Collaborating Clinics (SLICC)/ACR damage index was different according to the genotype. In conclusion, FcgammaRIIIA-176F/V polymorphism is not associated with SLE in Koreans.