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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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)].
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Case Reports
[Atypical antipsychotics and sexual dysfunction: five case-reports associated with risperidone].
Sexual and reproductive function side effects of atypical antipsychotics are frequent, often underestimated and badly tolerated. They contribute to the 50% rate of non-compliance reported for treated patients. Prevalence of sexual dysfunction associated with atypical antipsychotic treatment is high, varying from 18 to 96%. Atypical antipsychotics aren't, as a group, much better than typical antipsychotics, and among them, risperidone seems to induce more and quetiapine less sexual dysfunction. Most atypicals are non-selective, and have actions on multiple central and peripheral receptors. Among these, dopaminergic blockade could have a direct - altering motivation (desire) and reward (orgasm) - and an indirect negative influence on sexuality. Actually, the secondary hyperprolactinemia induced by some antipsychotics (typical antipsychotics, risperidone and amisulpiride), is dose-dependent, more pronounced for female patients, and may have a detrimental effect on sexual function. It also may result in hypogonadism, particularly for female patients. The long-term consequences of this secondary hypogonadism are subject to debate but potentially severe. Furthermore, the blocking and/or modulating actions of atypical antipsychotics on adrenaline, serotonine, histamine or acetyl-choline receptors all have the potential to contribute to secondary sexual problems. The pharmacological profile of risperidone, characterized by a strong affinity for D2 and alpha1 receptors, correlates with his tendency to significantly elevate prolactin levels and to produce ejaculatory disturbances. FIVE CASE-REPORTS: We describe five case-reports of sexual or hormonal disturbances associated with risperidone treatment: two cases of ejaculatory disturbance, one case of galactorrhea and two cases of amenorrhea. Alberto and David are two young male schizophrenic patients, treated with risperidone, and complaining of a total absence of ejaculation despite a preserved orgasm. Many recent case-reports describe the occurrence of retrograde ejaculation associated with risperidone but the exact prevalence is unknown. Retrograde ejaculation is thought to be related to the strong adrenolytic activity of risperidone. Alberto refused his medication because the ejaculatory dysfunction was unbearable for him. A switch to haloperidol depot was eventually well tolerated, without any sexual complaints. His case emphasizes the importance of sexual function for self-esteem and how this may amplify the intolerance to side-effects. David is on depot-risperidone in a setting of a legally forced treatment. Though he - reluctantly - accepts his medication, this side effect exacerbates his pre-existing delusions, strongly focused on sexual themes. His case illustrates how intolerance to sexual side-effects may be amplified by nature of delusions. Mireille is a 58 year old psychotic female patient, whose 2 mg risperidone treatment produced a unilateral galactorrhea. This sign became problematic because potentially visible at a time when Mireille started an activity in a sheltered occupation in town. Lowering dosage of antipsychotic allowed disappearance of the problem. Subjective responses to galactorrhea have been reported to be highly individual. Apart being a potentially visible side-effect, it may be misinterpreted as evidence of pregnancy or of a tumoral process. The cases of Ermina and Denise illustrate two contrasted situations in terms of subjective tolerability of reproductive function side-effects. Both were pre-menopausal patients with hyperprolactinemia secondary to risperidone treatment, resulting in amenorrhea. This was unbearable for Ermina. A switch to olanzapine allowed, one month later, the menses to resume. For Denise, on the other hand, the amenorrhea was a positive event, freeing her of unpleasant menses. ⋯ The described cases indicate that solving the problem is often possible, provided that individual preferences and subjective impact are taken in account. Antipsychotic treatment is often prescribed for very long periods. A better knowledge of - and attention to - the associated side effects, particularly on the sexual and reproductive functions, is necessary in order to reduce some potentially negative long-term effects and to improve the adherence to treatment of our patients.
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Elderly people and their family helpers are often isolated at home and do not have access to the professional psychological help that they require. For an elderly population, the trips to consulting rooms are difficult, tedious and expensive. Besides, maintaining a patient at home is heavy to manage for close relatives because of the organization, financial issues and above all the risk of psychological burnout. The literature shows us that psychological assistance is more common at distance from home, in hospitals, in special institutions or specific organizations. However, there is a clear need of help at home. We propose to develop psychological assistance at home for the patient/helper tandem in cases of dementia. This prospective study reports three different cases. ⋯ This prospective study leads us to the conclusion that the superposition of the frame of life and of the therapeutic frame represents a limit to psychotherapy but is not exclusive of psychological support at home. As a supplement to this face to face follow up at home, we could imagine other ways of providing such psychological support, by phone or by telemedicine for instance. Could the new technologies of communication help to compensate the lack of means in favour of the caregivers at home? Although these new technologies are more dedicated to institutions than to providing care at home, could they not be helpful for organizing psychological help at home? However, in order to validate such devices, they need to be fried and assessed at home.
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Despite immense importance of auditory verbal hallucinations (AVHs) in the phenomenology of schizophrenia, the neurocognitive and neurophysiological bases of AVHs remain obscure. On the neurocognitive level, it has been proposed that AVHs arise from the disordered monitoring manifested by patients' inability to recognize their inner speech as being their own. On the neurophysiological level, the AVHs have been attributed to the aberrant activity in the primary auditory cortex (Heschl's gyrus). Although interesting, these models cannot account for the very specific and restricted content of AVHs in individual patients. The specific content of AVHs persists across different psychotic episodes even after extended periods of remission. Furthermore, the AVHs are usually triggered by emotionally charged and stressful situations. ⋯ Finally, in contrast to our initial hypothesis we did not observe any significant differences between processing of the hallucinated versus non-hallucinated words in the primary auditory cortex. In retrospect, this result is not surprising because patients did not experience internally generated AVHs while in the scanner, but instead were exposed exclusively to externally generated stimuli.