A multimodal attempt to follow-up linkage regions using RNA expression, SNPs and CpG methylation in schizophrenia and bipolar disorder kindreds.

The complexity of schizophrenia (SZ) and bipolar disorder (BD) has slowed down progress in understanding their genetic roots. Alternative genomic approaches are needed to bypass these difficulties. We attempted a multimodal approach to follow-up on reported linkage findings in SZ and BD from the Eastern Quebec kindreds in chromosomes 3q21, 4p34, 6p22, 8p21, 8p11, 13q11-q14, 15q13, 16p12, and 18q21.

The Electroretinogram May Differentiate Schizophrenia From Bipolar Disorder.

Background: The retina is recognized as an approachable part of the brain owing to their common embryonic origin. The electroretinogram (ERG) has proved to be a valuable tool to investigate psychiatric disorders. We therefore investigated its accuracy as a tool to differentiate schizophrenia (SZ) from bipolar disorder (BP) even after balancing patients for their main antipsychotic medication.

Polygenic risk scores distinguish patients from non-affected adult relatives and from normal controls in schizophrenia and bipolar disorder multi-affected kindreds.

Recent studies have used results on SNP association with schizophrenia (SZ) and bipolar disorder (BD) to create polygenic risk scores (PRS) discriminating non-familial unrelated patients from controls. Little is known about the role of PRS in densely affected multigenerational families. We tested PRS differences between affected SZ and BD family members from their non-affected adult relatives (NAARs) in Eastern Quebec Kindreds and from controls.

The interaction of GSK3B and FXR1 genotypes may influence the mania and depression dimensions in mood disorders.

Background: Previous evidence in healthy subjects suggested that functional polymorphisms GSK3B rs12630592 and FXR1 rs496250 interact in regulating mood and emotional processing. We attempted to replicate this interaction primarily on manic and depressive dimensions in mood disorder patients, and secondarily on schizophrenia patients, diagnosis itself and age of onset.

Methods: Symptom dimensions were derived from the Comprehensive Assessment of Symptoms and History 82 items rated lifetime in acute episodes and stabilized interepisode intervals in 384 patients from the Schizophrenia and Bipolar Disorder Eastern Quebec Kindred Study.

Electroretinographic anomalies in medicated and drug free patients with major depression: Tagging the developmental roots of major psychiatric disorders.

The retina is tagged as an approachable part of the brain due to its common embryonic origin and appears as a promising site of investigation for psychiatric disorders. Retinal function is assessed best with the electroretinogram (ERG), which was obtained in a large sample of patients with major depressive disorder and matched controls. ERG cone and rod luminance response functions were recorded in non-dilated eyes in 100 major depressive disorder patients (MDD) and 100 controls, (mean age of 42.

Liability indicators aggregate many years before transition to illness in offspring descending from kindreds affected by schizophrenia or bipolar disorder.

Objectives: Offspring born to patients with affective and non-affective psychoses display indicators of brain dysfunctions that affected parents carry. Such indicators may help understand the risk trajectory.

Methods: We followed up the clinical/developmental trajectories of 84 young offspring born to affected parents descending from the Quebec kindreds affected by schizophrenia or bipolar disorder.

Cognitive structure from childhood to adulthood in kindreds densely affected by schizophrenia and bipolar disorder.

The developmental aspects of cognitive structures from childhood until adulthood and across different levels of risk for psychopathology have been little studied. The aim of the current study was to explore the cognitive factorial structure in subsamples from highly familial and densely affected kindreds of schizophrenia and bipolar disorder - i.e.

Childhood abuse and neglect may induce deficits in cognitive precursors of psychosis in high-risk children.

Background: Millions of children are born to parents affected by major psychoses. Cognitive dysfunctions seen in patients are already detectable in these children. In parallel, childhood maltreatment increases the risk of adult psychoses through unknown mechanisms.

Cluster analysis of cognitive deficits may mark heterogeneity in schizophrenia in terms of outcome and response to treatment.

Cognitive impairments are central to schizophrenia, but their clinical utility for tagging heterogeneity in lifetime outcome and response to treatment is not conclusive. By exploiting four cognitive domains consistently showing large deficits in studies, we tested whether cluster analysis would define separate subsets of patients and then whether the disease heterogeneity marked by these clusters would be related to lifetime outcome and response to treatment. A total of 112 schizophrenia patients completed a neuropsychological evaluation.

Follow-up of a major psychosis linkage site in 13q13-q14 reveals significant association in both case-control and family samples.

Background: We previously reported a genome-wide significant linkage for major psychosis in chromosome 13q13-q14.

Methods: An association analysis was conducted in 247 unrelated DSM-IV schizophrenia (SZ) patients and 250 unrelated control subjects from the Eastern Quebec population genotyped with 2150 single nucleotide polymorphisms in 13q13-q14. We also used the kindred sample where linkage was detected (125 SZ, 120 bipolar disorder [BD] and 36 schizoaffective disorder patients vs.

A protective-compensatory model may reconcile the genetic and the developmental findings in schizophrenia.

Objective: The neurodevelopmental, the multifactorial-oligogenic and the gene-environment diathesis models have provoked advances in schizophrenia research, yet the exact pathophysiology remains indefinable. We broadened our analysis of 20years of findings in adults and children descending from densely affected families in the Québec population with a founder effect. The goal was to inspect the link between these family-genetic and developmental findings.

Young offspring at genetic risk of adult psychoses: the form of the trajectory of IQ or memory may orient to the right dysfunction at the right time.

Objective: Neurocognitive dysfunctions analogous to those of adult patients have been detected in children at risk of schizophrenia and bipolar disorder. This led to the following developmental question: Do IQ and memory impairments exhibit different developmental courses from childhood to young adulthood in terms of stability or fluctuations?

Methods: In a high risk sample, we used a step by step sampling approach to narrow-down the early disease mechanisms. Upstream, we started with a 20-year follow-up of 48 densely affected multigenerational kindreds, including 1500 clinically characterized adult members.

Verbal and visual memory impairments among young offspring and healthy adult relatives of patients with schizophrenia and bipolar disorder: selective generational patterns indicate different developmental trajectories.

Objective: Memory deficits have been shown in patients affected by schizophrenia (SZ) and bipolar (BP)/mood disorder. We recently reported that young high-risk offspring of an affected parent were impaired in both verbal episodic memory (VEM) and visual episodic memory (VisEM). Understanding better the trajectory of memory impairments from childhood to adult clinical status in risk populations is crucial for early detection and prevention.

Ganglioside GM3 levels are altered in a mouse model of HIBM: GM3 as a cellular marker of the disease.

Objective: HIBM (Hereditary Inclusion Body Myopathy) is a recessive hereditary disease characterized by adult-onset, slowly progressive muscle weakness sparing the quadriceps. It is caused by a single missense mutation of each allele of the UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) gene, a bifunctional enzyme catalyzing the first two steps of sialic acid synthesis in mammals. However, the mechanisms and cellular pathways affected by the GNE mutation and causing the muscle weakness could not be identified so far.

N-glycan trimming by glucosidase II is essential for Arabidopsis development.

Glucosidase II, one of the early N-glycan processing enzymes and a major player in the glycoprotein folding quality control, has been described as a soluble heterodimer composed of alpha and beta subunits. Here we present the first characterization of a plant glucosidase II alpha subunit at the molecular level. Expression of the Arabidopsis alpha subunit restored N-glycan maturation capacity in Schizosaccharomyces pombe alpha- or alphabeta-deficient mutants, but with a lower efficiency in the last case.

Engineering of a sialic acid synthesis pathway in transgenic plants by expression of bacterial Neu5Ac-synthesizing enzymes.

Plants are a low-cost and contamination-free factory for the production of recombinant pharmaceutical proteins. However, plant-made pharmaceuticals differ from their mammalian homologues by the structure of their N-linked glycans. For instance, most mammalian glycoproteins harbour terminal sialic acids that control their half-life in the bloodstream.

Monoclonal C5-1 antibody produced in transgenic alfalfa plants exhibits a N-glycosylation that is homogenous and suitable for glyco-engineering into human-compatible structures.

Structural analysis of the N-glycosylation of alfalfa proteins was investigated in order to evaluate the capacity of this plant to perform this biologically important post-translational modification. We show that, in alfalfa, N-linked glycans are processed into a large variety of mature oligosaccharides having core-xylose and core alpha(1,3)-fucose, as well as terminal Lewis(a) epitopes. In contrast, expression of the C5-1 monoclonal antibody in alfalfa plants results in the production of plant-derived IgG1 which is N-glycosylated by a predominant glycan having a alpha(1,3)-fucose and a beta(1,2)-xylose attached to a GlcNAc2Man3GlcNAc2 core.

The gene expression and enzyme activity of plant 3-deoxy-D-manno-2-octulosonic acid-8-phosphate synthase are preferentially associated with cell division in a cell cycle-dependent manner.

3-deoxy-D-manno-2-octulosonic acid-8-phosphate (Kdo-8-P) synthase catalyzes the condensation of phosphoenolpyruvate with D-arabinose-5-phosphate to yield Kdo-8-P. Kdo-8-P is the phosphorylated precursor of Kdo, a rare sugar only found in the rhamnogalacturonan II pectic fraction of the primary cell walls of higher plants and of cell wall polysaccharides of some green algae. A cDNA named LekdsA (accession no.