Associations between purine metabolites and clinical symptoms in schizophrenia

Background: The antioxidant defense system, which is known to be dysregulated in schizophrenia, is closely linked to the dynamics of purine pathway. Thus, alterations in the homeostatic balance in the purine pathway may be involved in the pathophysiology of schizophrenia. Methodology/Principal Findings: Breakdown products in purine pathway were measured using high-pressure liquid chromatography coupled with a coulometric multi-electrode array system for 25 first-episode neuroleptic-naïve patients with schizophrenia at baseline and at 4-weeks following initiation of treatment with antipsychotic medication. Associations between these metabolites and clinical and neurological symptoms were examined at both time points. The ratio of uric acid and guanine measured at baseline predicted clinical improvement following four weeks of treatment with antipsychotic medication. Baseline levels of purine metabolites also predicted clinical and neurological symtpoms recorded at baseline; level of guanosine was associated with degree of clinical thought disturbance, and the ratio of xanthosine to guanosine at baseline predicted degree of impairment in the repetition and sequencing of actions. Conclusions/Significance: Findings suggest an association between optimal levels of purine byproducts and dynamics in clinical symptoms and adjustment, as well as in the integrity of sensory and motor processing. Taken together, alterations in purine catabolism may have clinical relevance in schizophrenia pathology

The relationship between membrane pathology and language disorder

Abstract Receptive language disorder in schizophrenia has been hypothesized to involve a fundamental deficit in the temporal (time-based) dynamics of brain function that includes disruptions to patterns of activation and synchronization. In this paper, candidate mechanisms and pathways that could account for this basic deficit are discussed. Parallels are identified between the patterns of language dysfunction observed for schizophrenia and dyslexia, two separate clinical disorders that may share a common abnormality in cell membrane phospholipids. A heuristic is proposed which details a trajectory involving an interaction of brain fatty acids and second-messenger function that modulates synaptic efficacy, and, in turn, influences language processing in schizophrenia patients. It is additionally hypothesized that a primary deficit of functional excitation originating in the cerebellum, in combination with a compensatory decrease of functional inhibition in the prefrontal cortex, influences receptive language dysfunction in schizophrenia.