Encephale
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Schizophrenia is a devastating psychiatric disorder with a broad range of behavioural and biologic manifestations. There are several clinical characteristics of the illness that have been consistently associated with poor premorbid adjustment, long duration of psychosis prior to treatment and prominent negative symptoms. The etiopathogenic mechanisms of lack of insight in patients with schizophrenia are to date unknown, although several hypotheses have been suggested. A point of convergence for the theoretical models occurs with regard to the neuronal membrane. Neuronal membrane contains a high proportion of polyunsaturated fatty acid and is the site for oxidative stress. Oxidative stress is a state when there is unbalance between the generation of reactive oxygen species and antioxidant defence capacity of the body. It is closely associated with a number of diseases including Parkinson's disease, Alzheimer-type dementia and Huntington's chorea. Accumulating evidence points to many interrelated mechanisms that increase production of reactive oxygen or decrease antioxidant protection in schizophrenic patients. ⋯ These results demonstrate altered membrane dynamics and antioxidant enzyme activity in schizophrenia. Membrane dysfunction can be secondary to free a radical-mediated pathology, and may contribute to specific aspects of the schizophrenia symptomatology. Membrane defects can significantly alter a broad range of membrane functions and presumably modify behavior through multiple downstream biological effects. Phospholipid metabolism in the brain may be perturbed in schizophrenia, with reduced amounts of phosphatidylcholins and phosphatidylethanolamine in post-mortem brain tissue from schizophrenic patients, and large amounts of lipofuscin-like materiel in the oligodendrocytes. The existence of these products within cell membranes results in an unstable membrane structure, altered membrane fluidity and permeability and impaired signal transduction. Recent findings suggest that multiple neurotransmitter systems may be faulty. CNS cells are more vulnerable to the toxic effects of free radicals because they have a high rate of catecholamine oxidative metabolic activity. Neurotransmitters, like glutamate, can induce the same metabolic processes that increase free radical production and can lead to impaired dopamine-glutamate balance. These results question the role of this imbalance in the biochemical basis evoked in the etipathogenic mechanisms of schizophrenia, as well as the role of antioxidants in the therapeutic strategy and their implication in preventive and early intervention approaches in populations at risk for schizophrenia.
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Depression is common in people with schizophrenia and is associated with substantial morbidity explaining also the considerable attention and recognition of this entity as suggested by the inclusion of the post-psychotic depression in DSM IV and ICD 10. The prevalence of this disorder varies according to the type of approach used (range between 7% to 75%). Prescription of antidepressants plus antipsychotic treatment is frequent in clinical practice (11 to 43%). ⋯ The results provide weak evidence for the efficacy of antidepressants in patients with schizophrenia and depression. Today, the only SSRI tested in the treatment of depression in schizophrenic patients is sertraline. One study led to positive results. Since the meta-analysis, one additional study has been performed comparing sertraline to placebo. No difference between the 2 treatment groups was demonstrated but the power of the trial was rather low. Further research is required to determine the best approach towards treating depression in patients with schizophrenia, with clinical trials performed for longer periods, using appropriate assessment criteria such as depressive symptoms and quality of life.
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Over the past decades, cognitive psychology contribution to our understanding of aging relies on two major perspectives, focusing on the selective impact of age on either cognitive multiple-systems or global factors of cognition: slowing, working memory and inhibition. In the latter, reduction in inhibitory control during aging (in its access, deletion or restraint functions) is associated with poorer performance on a variety of tasks referring to memory, comprehension or language [Hasher, Zacks and May (16)]. The attractiveness of inhibition as an explanatory factor results in part in the absence of negative priming during aging. Negative priming refers to the slow down of latencies when individuals have to respond to recently ignored informations, compared to unrelated informations. The dissociation, between a preserved location negative priming and an absence of identity negative priming during aging, supports the dorsal-ventral model of inhibition which suggests that spatial and identity inhibition are supported by different and independent visual pathways. An alternative model, directly at odds, is that inhibitory mechanisms are supported by the frontal lobe. In this perspective, inhibition is not a central process responsible for the control of working memory contents, but an automatic and local mechanism whose triggering depends on controlled attention. Therefore, working memory drives efficient inhibition by sustaining task instructions and appropriate responses throughout task execution. This hypothesis is consistent with Houghton and Tipper's (17) architecture of selective attention. According to the authors, the presence or absence of automatic inhibition is very closely linked to a Match/Mismatch field whose function is to compare the present stimulus to an internal self-generated internal template. When an information fails to match the subject's current goals, the match/mismatch field causes an automatic inhibitory imbalance which reduces the to-be-ignored properties' responsiveness. In contrast, information matching subjects' goal is enhanced through an automatic excitatory imbalance. The accurate functioning of the Match/Mismatch field requires efficient executive functioning responsible for the uphold of goals and correct responses. In the case of negative priming, manipulating the efficiency of working memory is of interest as it should affect the triggering of slowing, ie, an indirect inhibitory deficit, when the task is resource demanding [Conwayet al. (6)]. Moreover, if inhibition, as reflected by negative priming, is mediated by individual resource capacity, then NP should disappear during aging only when individuals are engaged in a resource-demanding task. ⋯ The implications of our data are consistent with the level of processing account, as well as the recent neuroimaging contributions which suggest, for example, the involvement of the dorso-lateral prefrontal cortex (sensitive to aging) when task demands are high, and a ventro-lateral prefrontal implication when demands are low [see Eenshuistra et al. for a review (10)].