Epigenetics, or alterations in the phenotype or gene expression due to mechanisms other than changes in the underlying DNA sequence, reflects the sensitivity and responsiveness of human and animal brains in constantly varying circumstances regulating gene expression profiles that define the biomarkers and present the ultimate phenotypical outcomes, such as cognition and emotion. Epigenetics is associated with functionally relevant alterations to the genome in such a fashion that under the particular conditions of early, adolescent, and adult life, environmental signals may activate intracellular pathways that remodel the "epigenome," triggering changes in gene expression and neural function. Thus, genetic influences in neuropsychiatric disorders that are subject to clinical staging, epigenetics in schizophrenia, epigenetic considerations in the expression of sensorimotor gating resulting from disease conditions, biomarkers of drug use and addiction, current notions on the role of dopamine in schizophrenia spectrum disorders, and the discrete interactions of biomarkers in persistent memory were to greater or lesser extents reflected upon. The relative contributions of endophenotypes and epistasis for mediating epigenetic phenomena and the outcomes as observed in the analysis of biomarkers appear to offer a multitude of interactive combinations to further complicate the labyrinthine machinations of diagnosis, intervention, and prognosis.
"Assuming that the pathology of the schizophrenia [119, 120] and the cell proliferation/neurogenesis [70, 121] are subjected to epigenetic control mechanisms, future research is needed to address the exact neurogenic mechanisms of antipsychotics adjusting by epigenetic factors. "
[Show abstract][Hide abstract] ABSTRACT: Schizophrenia is a complex psychiatric disorder. Although a number of different hypotheses have been developed to explain its aetiopathogenesis, we are far from understanding it. There is clinical and experimental evidence indicating that neurodevelopmental factors play a major role. Disturbances in neurodevelopment might result in alterations of neuroanatomy and neurochemistry, leading to the typical symptoms observed in schizophrenia. The present paper will critically address the neurodevelopmental models underlying schizophrenia by discussing the effects of typical and atypical antipsychotics in animal models. We will specifically discuss the vitamin D deficiency model, the poly I:C model, the ketamine model, and the postnatal ventral hippocampal lesion model, all of which reflect core neurodevelopmental issues underlying schizophrenia onset.
"However, while there has been substantial progress towards this aim, sensitivity and specificity issues make this a future goal rather than a current reality and our classifications remain based on clinical symptoms. Both genetic (Archer et al., 2010) and endophenotypic staging markers, including changes in brain anatomy (Pantelis et al., 2009), neurotrophic, and pro-apoptotic factors (Kapczinski et al., 2009) and other endophenotypes, have been found, and some studies have found neurobiological correlates between different stages of the same psychiatric illness. However, the use of such correlates is hampered by their relatively low sensitivity and poor specificity. "
[Show abstract][Hide abstract] ABSTRACT: The concept of staging of disease in psychiatry has developed over the past years. A neglected component of this model pertains to people in the advanced stages of a mental illness, who remain symptomatic and functionally impaired despite treatment. These patients are often high service utilizers, receiving complex multimodal treatments where the balance of risk and benefit shifts perceptibly. In this paper, we argue the need to adopt 'palliative' models of care for some individuals, and consider changing the therapeutic goals to follow care pathways similar to those used in other chronic and refractory medical illnesses.
Data was sourced by a literature search using Medline and a hand search of scientific journals. Relevant articles were selected.
Clinical staging can help us better define subgroups of patients who will benefit from different goals and treatment. In the most advanced stage group, we find patients with persistent symptoms and treatment resistance. In these situations, it may be preferable to follow some of the principles of palliative care, which include the setting of attainable goals, reduction of side-effects, limited symptom control, targeting identified psychological and social problems, and attempting to attain the best quality of life for these patients and their families.
It is in the interest of those in the advanced phases of a disorder that clinicians acknowledge the limitations of treatment and actively attempt to plan treatment utilizing alternate models. It is essential to be clear that such approaches do not equate to the abandonment of care, but rather to the reconceptualizing of feasible and personalized treatment goals, a rebalancing of the risks and benefits of intervention, the management of illness behaviour, and the approaches that allow the patient to live gainfully within their limitations.
Australian and New Zealand Journal of Psychiatry 02/2012; 46(2):92-9. DOI:10.1177/0004867411432072 · 3.41 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Neurodevelopmental risk factors have assumed a critical role in prevailing notions concerning the etiopathogenesis of neuropsychiatric disorders. Staging, diagnostic elements at which phase of disease is determined, provides a means of conceptualizing the degree and extent of factors affecting brain development trajectories, but is concurrently specified through the particular interactions of genes and environment unique to each individual case. For present purposes, staging perspectives in neurodevelopmental aspects of the disease processes are considered from conditions giving rise to neurodevelopmental staging in affective states, adolescence, dopamine disease states, and autism spectrum disorders. Three major aspects influencing the eventual course of individual developmental trajectories appear to possess an essential determinant influence upon outcome: (i) the type of agent that interferes with brain development, whether chemical, immune system activating or absent (anoxia/hypoxia), (ii) the phase of brain development at which the agent exerts disruption, whether prenatal, postnatal, or adolescent, and (iii) the age of expression of structural and functional abnormalities. Clinical staging may be assumed at any or each developmental phase. The present perspective offers both a challenge to bring further order to diagnosis, intervention, and prognosis and a statement regarding the extreme complexities and interwoven intricacies of epigenetic factors, biomarkers, and neurobehavioral entities that aggravate currents notions of the neuropsychiatric disorders.
Neurotoxicity Research 03/2010; 18(3-4):287-305. DOI:10.1007/s12640-010-9162-6 · 3.54 Impact Factor
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