Early visual processing deficits in dysbindin-associated schizophrenia.

Background: Variation at the dysbindin gene (DTNBP1) has been associated with increased risk for schizophrenia in numerous independent samples and recently with deficits in general and domain-specific cognitive processing. The relationship between dysbindin risk variants and sensory-level deficits in schizophrenia remains to be explored. We investigated P1 performance, a component of early visual processing on which both patients and their relatives show deficits, in carriers and noncarriers of a known dysbindin risk haplotype.

D-amino acid oxidase (DAO) genotype and mood symptomatology in schizophrenia.

A series of genetic studies have identified the D-amino acid oxidase (DAO) gene as potentially contributing to schizophrenia susceptibility. An interacting gene, D-amino acid oxidase activator (DAOA) has also been implicated and it has been suggested that variation at these genes may influence the efficiency of glutamate gating at N-methyl-D-aspartate-type (NMDA) receptors. However, recent data suggests that DAOA may influence susceptibility to mood episodes across the spectrum of psychotic disorders rather than contributing to a specific psychosis phenotype.

Functional genomics and schizophrenia: endophenotypes and mutant models.

This article summarizes the rationale, methods, and results of gene discovery programs in schizophrenia research and describes functional methods of investigating potential candidate genes. It focuses next on the most prominent current candidate genes and describes (1) evidence for their association with schizophrenia and research into the function of each gene; (2) investigation of the clinical phenotypes and endophenotypes associated with each gene, at the levels of psychopathologic, neurocognitive, electrophysiologic, neuroimaging, and neuropathologic findings; and (3) research into the ethologic, cognitive, social, and psychopharmacologic phenotype of mutants with targeted deletion of each gene. It examines gene-gene and gene-environment interactions.

Dysbindin (DTNBP1) and the biogenesis of lysosome-related organelles complex 1 (BLOC-1): main and epistatic gene effects are potential contributors to schizophrenia susceptibility.

Background: The DTNBP1 gene, encoding dysbindin, has been strongly implicated in schizophrenia (SZ) susceptibility by a series of independent genetic association and gene expression studies. Among its known functions, dysbindin is part of a protein complex, termed the biogenesis of lysosome-related organelles complex 1 (BLOC-1), the molecular components of which might be involved in the regulation of vesicular trafficking and dendrite branching.

Methods: A systematic investigation of the other seven BLOC-1 genes (MUTED, PLDN, CNO, SNAPAP, BLOC1S1, BLOC1S2, and BLOC1S3) for evidence of association with SZ was undertaken in a sample of 373 SZ cases and 812 control subjects.

Evidence for association and epistasis at the DAOA/G30 and D-amino acid oxidase loci in an Irish schizophrenia sample.

The D-amino acid oxidase (DAO) signaling pathway has been implicated in schizophrenia pathogenesis. This may be mediated through modulation of NMDA function by DAO, which is in turn activated by DAO activator (DAOA, formerly G72). Chumakov et al.

Sialic acids: carbohydrate moieties that influence the biological and physical properties of biopharmaceutical proteins and living cells.

Sialic acids are structurally diverse molecules that have important roles in the physiological reactions and characteristics of prokaryotes and eukaryotes. These include the ability to mask epitopes on underlying glycan chains and to repulse negatively charged moieties. Here, we describe the metabolism and immunological relevance of sialic acids and outline how their properties have been exploited by the pharmaceutical industry to enhance the therapeutic properties of proteins such as asparaginase and darbepoetin alpha.

Do antisaccade deficits in schizophrenia provide evidence of a specific inhibitory function?

Background: Despite its inhibitory control requirements, antisaccade deficits have been consistently associated with working memory impairments in schizophrenia. We investigated whether variance in antisaccade performance could be better accounted for in terms of a specific inhibitory function.

Method: We assessed 48 clinically stable out-patients with schizophrenia on an antisaccade task, as well as on measures of spatial and verbal working memory, sustained selective attention, and a simple motoric go/no-go measure of response inhibition.

Variance in neurocognitive performance is associated with dysbindin-1 in schizophrenia: a preliminary study.

Susceptibility genes for schizophrenia have been hypothesised to mediate liability for the disorder at least partly by influencing cognitive performance. We investigated the association between genotype and cognitive performance for a Dysbindin risk haplotype which is associated with schizophrenia in our sample. Fifty-two patients with schizophrenia or schizoaffective disorder (24 risk haplotypes carriers versus 28 non-risk haplotype carriers) were assessed in areas of cognition showing evidence of familial deficits in schizophrenia.

Are deficits in executive sub-processes simply reflecting more general cognitive decline in schizophrenia?

Background: Schizophrenia is associated with both global and specific cognitive deficits. We sought to investigate whether deficits in executive subcomponents differed in their relationship to global cognitive impairments.

Method: 95 patients were classified according to pre-morbid and current general cognitive ability as having either (a) intact pre-morbid and current general cognitive ability; (b) intact pre-morbid but deteriorated current ability, and (c) deteriorated both pre-morbid and current cognitive ability.

Evidence that specific executive functions predict symptom variance among schizophrenia patients with a predominantly negative symptom profile.

Introduction: Although deficits in executive functioning in schizophrenia have been consistently reported, their precise relationship to symptomatology remains unclear. Recent approaches to executive functioning in nonschizophrenia studies have aimed to "fractionate" the individual cognitive processes involved. In this study, we hypothesised that if these processes are fractionable, then particular symptom syndromes may be selectively related to executive deficits.

Are the cognitive deficits associated with impaired insight in schizophrenia specific to executive task performance?

Although impaired insight in schizophrenia has been associated with deficits in executive task performance, the relationship remains unclear. We aimed to clarify this relationship by fractionating executive functioning into the theoretically derived functions of inhibition, working memory, set shifting, and sustained attention. We compared the performance of patients showing impaired insight, patients showing good insight, and a matched control group on measures of each of these executive functions, along with measures of current cognitive functioning and memory.

Investigation of the apolipoprotein-L (APOL) gene family and schizophrenia using a novel DNA pooling strategy for public database SNPs.

We performed an extensive genetic association study of the six known apolipoprotein-L (APOL) genes and schizophrenia (SZ) using a novel DNA pooling strategy. The APOL genes are both positional and functional candidate genes for SZ. This gene family maps to chromosome 22q12.

Evidence that health attributions and symptom severity predict insight in schizophrenia.

Although a relationship between insight and symptomatology in schizophrenia has been repeatedly demonstrated, the influence of psychological variables such as coping mechanisms and attributional style is less clear. We evaluated health attributions, subjective resources for coping, symptomatology, general cognitive functioning, and insight among 38 consecutive admissions with DSM-III-R schizophrenia from a geographically defined catchment area. Health attributions accounted for a significant amount of insight even after symptom severity was accounted for and together predicted 32% of variation in insight scores.

Compliance therapy: a randomised controlled trial in schizophrenia.

Objective: To evaluate the efficacy of "compliance therapy" for improving adherence to prescribed drug treatment among patients with schizophrenia.

Design: Randomised controlled trial.

Setting: Urban catchment area psychiatric service.

Can specific deficits in executive functioning explain the negative symptoms of schizophrenia? A review.

The relationship between clinical symptoms and neurocognitive impairment has been a growing interest in the field of schizophrenia research. We review the empirical evidence for whether some schizophrenia symptoms can be viewed as expressions of disordered executive functioning. A specific focus of our review is Frith's (1992) neurocognitive theory of negative symptoms, and whether this theory is supported by studies of executive functioning in schizophrenia.

Predictors of compliance with neuroleptic medication among inpatients with schizophrenia: a discriminant function analysis.

Objective: To identify clinically useful predictors of adherence to medication among persons with schizophrenia.

Method: We evaluated levels of compliance with neuroleptic medication among 32 consecutive admissions with DSM-III-R schizophrenia from a geographically defined catchment area using a compliance interview. We also assessed symptomatology, insight, neurological status and memory.

Rapid single-tube screening of the C282Y hemochromatosis mutation by real-time multiplex allele-specific PCR without fluorescent probes.

Background: An accurate determination of the major HFE mutation (C282Y), which is associated with hereditary hemochromatosis, is important in diagnosis and risk assessment for this disease. We report a single-tube high-throughput PCR method for the detection of C282Y.

Methods: We combined three previously described principles: allele-specific PCR, mutagenically separated PCR, and amplicon identification by specific dissociation curves.