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. The PANSS, GAF-S and GAF-F were rated at the onset and endpoint of the illness trajectory. A blind judgment of the lifetime response to treatment was made. The first cluster presented near-normal cognitive performance. Two other clusters of severely impaired patients were identified: one generally impaired in the four cognitive domains and another selectively impaired in visual episodic memory and processing speed, each relating to a different lifetime evolution of disease and treatment response. Although the two impaired clusters were clinically indistinguishable in symptom severity and functioning at disease onset, patients with selective cognitive impairments demonstrated better improvement at outcome, whereas the generally impaired patients were more likely to be treatment refractory. The findings have implications for the management of patients and for clinical trials since particular combinations of cognitive deficits in patients would influence their treatment response.

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. In multigenerational families densely affected by SZ or BP, our aim was to compare the memory impairments observed in young nonaffected offspring with memory functioning in nonaffected adult relatives and patients. Methods: For 20 years, we followed up numerous kindreds in the Eastern Québec population. After having characterized the Diagnostic and Statistical Manual of Mental Disorders phenotypes, we assessed cognition (N = 381) in 3 subsamples in these kindreds and in controls: 60 young offspring of a parent affected by SZ or BP, and in the adult generations, 92 nonaffected adult relatives and 40 patients affected by SZ or BP. VEM was assessed with the California Verbal Learning Test and VisEM with the Rey figures. Results: The VEM deficits observed in the offspring were also found in adult relatives and patients. In contrast, the VisEM impairments observed in the young offspring were present only in patients, not in the adult relatives. Conclusion: Implications for prevention and genetic mechanisms can be drawn from the observation that VEM and VisEM would show distinct generational trajectories and that the trajectory associated with VisEM may offer a better potential than VEM to predict future risk of developing the disease.

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SummaryStructural 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 α (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 IgG 1 which is N-glycosylated by a predominant glycan having a α (1,3)-fucose and a β (1,2)-xylose attached to a GlcNAc 2 Man 3 GlcNAc 2 core.Since this core is common to plant and mammal N-linked glycans, it therefore appears that alfalfa plants have the ability to produce recombinant IgG 1 having a N-glycosylation that is suitable for in vitro or in vivo glycan remodelling into a human-compatible plantibody.For instance, as proof of concept, in vitro galactosylation of the alfalfa-derived C5-1 mAb resulted in a homogenous plantibody harbouring terminal β (1,4)-galactose residues as observed in the mammalian IgG.

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