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The need for individualised antipsychotic drug therapy in patients with schizophrenia
No full textDrug therapy for schizophrenia aims to both reduce symptoms in the acute phase and maintain long-term symptomatic remission during periods of stabilization. Atypical antipsychotic agents are the mainstay of schizophrenia therapy because of their improved tolerability, including a reduced likelihood of extrapyramidal symptoms, compared with conventional antipsychotics. However, responses to antipsychotic therapy are influenced by a wide range of factors, such as age, gender, race, comorbidities, genetics and social and environmental conditions, that make identifying the most appropriate antipsychotic treatment for each individual patients, an ongoing challenge for physicians. Tools that may be useful to assist clinicians in determining appropriate individual therapy include consideration of treatment moderators, which specify for whom or under what conditions a treatment works, treatment mediators, which are mechanisms by which a treatment achieves its effects, and cluster group analyses, which identify subsets of patients with similar characteristics. Further research is required to determine whether cluster groups of patients with schizophrenia can be identified based on treatment moderators and mediators, and whether antipsychotic prescribing based on consideration of these cluster groups leads to improved treatment outcomes
Clinical implications of dopamine research in schizophrenia
No full textOne of the most stimulating problems posed by second generation antipsychotics is the question of whether their ability to act on the negative, as well as the positive, symptoms of schizophrenia relies on the same neurochemical mechanisms as those responsible for their lack of extrapyramidal symptoms (EPS). Amisulpride is a substituted benzamide antipsychotic, which is known to be efficacious against both the positive and the negative symptoms of schizophrenia and to have a lower propensity to induce EPS than conventional antipsychotics. Amisulpride preferentially blocks the D2 and D3 subtypes of dopamine receptors, both presynaptically in the frontal cortex, enhancing dopaminergic transmission, and postsynaptically in subcortical areas such as the nucleus accumbens, so reducing dopaminergic transmission. Given that dopaminergic under-activity in the frontal cortex is thought to produce negative symptoms, and over-activity in the limbic system to produce positive symptoms, it is proposed that these are the mechanisms by which amisulpride produces its atypical profile. © 2002 Informa UK Ltd All rights reserved
Is there an evolutionary mismatch between the normal physiology of the human dopaminergic system and current environmental conditions in industrialized countries?
No full textA large body of evidence has recently defined a field theory known as 'evolutionary mismatch', which derives its attributes largely from the fact that current environmental conditions are completely different from those in which the human central nervous system evolved. Current views on the evolutionary mismatch theory lack, however, any attempts to define which brain areas or neuronal circuits should be mostly involved in coding such misevolved traits and to what extent our neurobiological knowledge can be applied to the topographical localization of a specific psychopathology. In this respect the mesocorticolimbic dopaminergic circuits have long been misconceptualized as simple reward or reinforcement systems. Instead, they motivate and coordinate the functions of the higher brain areas that mediate planning and foresight and direct finalized movement in both animals and humans. These systems make animals intensely interested in exploring the world around them, but by the same means they also make them susceptible to the environmental stimuli that have been sought and consumed. It is has been speculated that the cortical dopamine targets that developed most recently in phylogeny are of particular functional value, and that the mesocorticolimbic dopaminergic system is involved in more complex integrative functions than previously assumed. In the present paper I will argue that some mental disorders may have their deep roots in the evolutionary mismatch between the normal physiology of the mesocorticolimbic dopaminergic system and the current environmental conditions in affluent societies
WHAT DARWIN COULD TEACH US TODAY ABOUT MODERN VACCINES AND THEIR HEALTH POLICIES
No full textThe recurring questions are whether the new variants are more efficient in replicating, transmitting, or causing damage to the host, or if they will escape, as changed in antigenic conformations, immune responses trained naturally by infection with the virus or artificially by vaccines. These are questions pertaining to Darwinian immunology and vaccinology
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