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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Over the last 20 years research has convincingly demonstrated that the illness, schizophrenia, is amenable to social and environmental influence (Leff et al. 1982; Falloon et al. 1985; Hogarty et al. 1986). The impetus for the research is the fact that, at best, genetic inheritance explains only 70% of the disorder's aetiology. The findings of the studies allow certain basic but important principles to be formulated. These are that some people inherit a genetic predisposition or "vulnerability" to schizophrenia which develops either in response to the acute stress of "life events" or the chronic stress encountered in some families. Originally the term "Expressed Emotion" was coined to describe emotional atmosphere at home which was thought to consist particularly of criticism, hostility or emotional over-involvement (Brown et al. 1962). Intervention strategies have arisen from the studies which demonstrates that stress in families caring for a relative with schizophrenia can be reduced, leading to not only a smaller risk of relapse in the relative with the illness, but also an improvement in the carer's own mental health status (Tarrier et al. 1988). Intervention consists of health education for carers and family stress management techniques which may help to lessen over-stimulation in family life. Community Psychiatric Nurses (CPNs) are a rapidly expanding sector of most mental health service provision in the United Kingdom but the evidence is that their role with the sufferer from schizophrenia consists largely of the administration of depot medication and very little else.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A new role for the community psychiatric nurse in working with families caring for a relative with schizophrenia. 228 14

The dexamethasone suppression test (DST) was performed in 21 drug-free schizophrenic patients. The patients satisfied DSM-III and Research Diagnostic Criteria for schizophrenia and were in an acute phase of the disease. In 15 of the patients the DST was repeated after about 5 weeks of treatment with neuroleptics. DST compliance was checked by analysis of dexamethasone concentrations in plasma. In the acute phase 71% (at 04 p.m.) of the patients were nonsuppressors. After neuroleptic treatment the frequency of abnormal responders had decreased to 20%. The decrease in nonsuppressors was not due to alteration of the dexamethasone concentration between the two test occasions. Prolactin levels were markedly increased at the second test occasion compared with the first. There were no significant relationships between cortisol levels, cortisol suppression and prolactin levels. The high frequency of nonsuppressors among schizophrenic patients in the acute phase of the disease indicates that acute stress may be a confounding factor in the outcome of DST.
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PMID:Dexamethasone suppression test in schizophrenic patients before and during neuroleptic treatment. 287 44

Psychological factors have long been thought to play a contributing role in either the predisposition, onset or course of various physical illnesses. Recently, rapid advances in immunology have created interest in the interaction between psychosocial factors, behaviour and the immune system. This paper reviews some of the models proposed to explain the relationship between psychological variables and physical illness and presents evidence for a contribution of psychological factors to certain illnesses in which abnormalities in immunologic state are thought to be important. From a somewhat different perspective, animal studies have demonstrated complex effects of stress, on disease susceptibility. Recent human studies have demonstrated consistent immunologic changes in people undergoing acute naturally occurring psychological stress such as bereavement or an important examination. In humans, the effects of chronic stress may be different from acute stress, corresponding to the findings in animals. Abnormalities in immunologic functioning and physical illness are reviewed for different psychiatric disorders--depression, anorexia nervosa and schizophrenia; depression is the only disorder which consistently demonstrated immunologic changes. Possible mechanisms for the stress/immune-change relationship are suggested.
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PMID:Stress, immunity and illness--a review. 360 31

Data from two studies, one naturalistic and the other a controlled trial, were analysed to clarify the relationships between independent life events. Expressed Emotion of a key relative, maintenance neuroleptics and the relapse of schizophrenia. It was found that patients in the community who are unprotected by medication are vulnerable either to acute stress in the form of life events or to chronic stress in the form of living with a high Expressed Emotion relative. Patients on regular medication are protected against one or other stress, but are very likely to relapse if the two forms of stress occur together. A model of schizophrenic susceptibility to environmental stress is constructed to incorporate these observations.
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PMID:Life events, relatives' expressed emotion and maintenance neuroleptics in schizophrenic relapse. 614 82

It is suggested that there exists a competitive antagonist of the cholinergic system which is secreted during sleep, pregnancy, and acute stress. A biochemical model of the sleep cycle is presented. It is suggested that normally the putative cholinergic antagonist is metabolized rapidly upon being released from the cholinergic receptor. Defective metabolism of this putative cholinergic antagonist is hypothesized to be one cause of hypotonic schizophrenia.
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PMID:Resolved: there exists an atropinic agent in vivo. 744 86

The response of the central nervous system to stress is often critical to the adaptation of an organism to its environment. However, in humans the response to stress also can be maladaptive, resulting in the expression or exacerbation of many neurological and psychiatric disorders. In this review, we examine the impact of stress on the synthesis and release of dopamine within mesocortical, mesoaccumbens, and nigrostriatal dopamine projections. We note that whereas stress increases the neurochemical activity of each of these populations of dopamine neurons, heterogeneities do exist. Specifically, acute stress evokes a greater increase in dopamine metabolism and release within the prefrontal cortex than the subcortical sites. Furthermore, whereas prior exposure to chronic stress enhances the response of mesocortical dopamine neurons to an acute novel stressor, this does not occur in the subcortical sites. In addition to these regional heterogeneities, we also note that even within a single dopamine projection there can be heterogeneous regulation of dopamine synthesis and release. Specifically, whereas stress-induced dopamine release in the neostriatum is mediated by an action of glutamate on the dopamine cell body, stress-induced dopamine synthesis in the neostriatum is mediated by an action of glutamate on the dopamine nerve terminal. Finally, we propose that regional heterogeneities in the responsiveness of central dopamine neurons to stress may ultimately play a role in the expression and exacerbation of symptoms associated with schizophrenia.
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PMID:The effects of stress on central dopaminergic neurons: possible clinical implications. 935 11

The effects of acute and repeated nicotine administration on the stress response of rat mesoprefrontal dopaminergic pathways were examined. Rats were given daily injections of nicotine (0.15 or 0.60 mg/kg, s.c., freebase) or saline for 4 days, then challenged with either nicotine or saline. A regimen of inescapable electrical footshocks or no footshocks was then administered. Thirty minutes after final injection, rats were sacrificed, brains removed and dopamine (DA) and its metabolite dihydroxy-O-phenylacetic acid (DOPAC) were extracted from medial prefrontal cortex (mPFC), nucleus accumbens septi (NAS) and dorsolateral striatum and quantified by high performance liquid chromatography with electrochemical detection. Acute administration of low dose nicotine (0.15 mg/kg) produced an increase in DA utilization (increased DOPAC/DA ratio) in mPFC and NAS, but not striatum. High dose nicotine (0.60 mg/kg) produced activation in NAS, but not mPFC or striatum. Repeated low dose nicotine pre-treatment produced tolerance to the effects of nicotine challenge in the mPFC, and reduced its effects in NAS. Footshock stress preferentially increased DA utilization in mPFC and associated footshock stress-induced immobility responses, and these were reduced by low, but not high, dose repeated nicotine pre-treatment. Further, a single dose of the nicotinic acetylcholine receptor (nAChR) antagonist mecamylamine (MCA) 30 min prior to nicotine challenge dose-dependently blocked the reduction of mesoprefrontal DA stress responsivity and immobility responses produced by repeated nicotine pre-treatment. These results indicate that: (1) there are dose-dependent differential effects of acute and repeated nicotine pre-exposure on regional DA utilization; (2) low, but not high, dose repeated nicotine reduces both the mesoprefrontal DA and behavioral effects of acute footshock stress; and (3) these effects of repeated nicotine may depend on mecamylamine-sensitive nAChR stimulation. These results may have relevance to acute stress and nicotine dependence, particularly in schizophrenic disorders, which have high prevalence rates of co-morbid nicotine dependence, stress-induced symptom exacerbation and prefrontal cortical dysfunction.
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PMID:Effects of repeated nicotine pre-treatment on mesoprefrontal dopaminergic and behavioral responses to acute footshock stress. 972 61

This review covers some recent findings of the electrophysiological mechanisms through which mesocortical dopamine modulates prefrontal cortical neurons. Dopamine has been shown to modulate several ionic conductances located along the soma-dendritic axis of prefrontal cortical pyramidal neurons. These ionic currents include high-voltage-activated calcium currents and slowly inactivating Na+ and K+ currents. They contribute actively in processing functionally segregated inputs during synaptic integration. In addition, dopamine mainly depolarizes the fast-spiking subtype of local GABAergic interneurons that connect the pyramidal neurons. This latter action can indirectly control pyramidal cell excitability. These electrophysiological data indicate that the actions of dopamine are neither "excitatory" nor "inhibitory" in pyramidal prefrontal cortex neurons. Rather, the actions of dopamine are dependent on somadendritic loci, timing of the arrival of synaptic inputs, strength of synaptic inputs, as well as the membrane potential range at which the PFC neuron is operating at a given moment. Based on available electrophysiological findings, a neuronal model of the pathophysiology of schizophrenia is presented. This model proposes that episodic hypo- and hyperactivity of the PFC and the associated dysfunctional mesocortical dopamine system (and their interconnected brain regions) may coexist in the same schizophrenic patient in the course of the illness. We hypothesize that the dysfunctional mesocortical dopamine input to the PFC may lead to abnormal modulation of ionic channels distributed in the dendritic-somatic compartments of PFC pyramidal neurons that project to the ventral tegmental area and/or nucleus accumbens. In some schizophrenics, a reduction of mesocortical dopamine to below optimal levels and/or a loss of local GABAergic inputs may result in a dysfunctional integration of extrinsic associative inputs by Ca2+ channel activity in the distal dendrites of PFC pyramidal neurons. This may account for the patients' distractibility caused by their inability to focus only on relevant external inputs. In contrast, in acute stress or psychotic episodes, an associated abnormal elevation of mesocortical dopamine transmission may greatly influence distal dendritic Ca2+ channel-mediated signal-processing mechanisms. This can enhance possible reverberative activity between adjacent interconnected pyramidal neurons via the effects of dopamine on the slowly inactivating Na+, K+, and soma-dendritic Ca2+ currents. The effects of high levels of PFC dopamine in this case may contribute to behavioral perseveration and stereotypy so that the patients are unable to use new external cues to modify ongoing behaviors.
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PMID:Developing a neuronal model for the pathophysiology of schizophrenia based on the nature of electrophysiological actions of dopamine in the prefrontal cortex. 1043 66

The neonatal (PND 7) lesion of the ventral hippocampus (VH) with ibotenic acid represents a well-established experimental paradigm that recapitulates many schizophrenia-like phenomena. In order to investigate molecular changes that could contribute to long lasting consequences on brain function, we have investigated the effects of the VH lesion on the expression for the trophic factors FGF-2 and BDNF. We used RNase protection assay to measure their mRNA levels in cortical regions of prepubertal (PND 35) and young adult (PND 56) animals, both under basal condition as well as in response to an acute restraint stress. The expression of BDNF was not altered by the VH lesion in prefrontal (PFC) and frontal cortex (FC) of PND 35 or PND 56 rats. An acute restraint stress at PND 35 produced a significant increase of the neurotrophin expression in PFC of sham as well as lesioned animals. However in young adult animals a significant elevation of BDNF expression was observed only in sham rats. We also found that the VH lesion produced a significant reduction of basal BDNF mRNA levels in the cingulate cortex of young adult, but not prepubertal rats. This effect was not accompanied by changes in the acute modulation of the neurotrophin, which was up-regulated by stress in both experimental groups. Conversely the expression of FGF-2 at PND 35 and PND 56 was not altered by early postnatal VH lesion, and there were no major differences between sham and lesioned animals in response to the acute stress. The changes in trophic factor expression may be relevant for the long-term effects of VH lesion on synaptic plasticity and may determine an increased vulnerability of the brain under challenging situations.
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PMID:Developmental and stress-related changes of neurotrophic factor gene expression in an animal model of schizophrenia. 1132 96

Although final brain size and the number of available neurons and axons appear to be established early in infancy, plasticity of the brain continues during adolescence through an integrated process of overproduction and elimination of synapses and receptors. In addition, hormonal levels change dramatically during this period, as a result of the onset of puberty. This age-specific condition has been suggested to serve as a permissive factor for the emergence of a number of early-onset neuropsychiatric disorders, including schizophrenia, attention-deficit hyperactivity disorder (ADHD), and perhaps substance abuse. However, relatively few investigations have focused on animal models of this developmental phase. The periadolescent rodent (similar30-45-day-old), has been proposed as a useful model. Periadolescent rats and mice are generally associated with a peculiar behavioral profile, consisting of basal hyperactivity, high attraction towards novel stimuli and a marked involvement in affiliative and playful behaviors. Moreover, a unique profile of psychopharmacological responsivity characterizes rodents around this age. Recent experiments by our group investigated age-related discontinuities in the response of the hypothalamic-pituitary-adrenal axis (HPA) to both stress and psychostimulants. The latter are often administered as therapeutic drugs to children with ADHD, which have been also associated with an impaired response to stress and abnormalities in HPA axis function. Indeed, an altered functioning of the HPA axis has been proposed as a possible risk factor and a potential marker for such a behavioral vulnerability. Animals were studied at adulthood (> pnd 70) or during periadolescence. Experiment I characterized basal corticosterone (CORT) levels in naive mice kept undisturbed in standard social conditions from weaning to sacrifice. Periadolescent male mice showed higher basal CORT levels than adult subjects, suggesting that the set up of the HPA axis is physiologically elevated during adolescence. In experiment II, we investigated age-related differences in the response to both acute and chronic stress conditions. Periadolescent and adult mice were housed either in a standard (three animals per cage) or in a crowding condition (nine animals per cage). The latter has been indeed reported to potentiate the subsequent reaction to acute stress in adult rodents. At the end of this period and following 24 h individual housing, mice were injected with either saline (SAL) or a standard amphetamine (AMPH) dose (2 mg/kg), and faced with a mild acute psychological stress, namely removal of sawdust from the home cage. Important sex differences emerged in animals of the two ages. Periadolescent females showed a reduced CORT response to acute stress. Within the adult male group, the chronic crowding condition produced a prominent potentiation of CORT response to the acute stress challenge. Conversely, this profile was not evidenced in periadolescents. These results indicate a strong role for gender and social variables in the response of periadolescent subjects to the various aspects of stress. As for AMPH effects, in the absence of significant changes in adult subjects, the drug produced a marked CORT release in periadolescent mice. A better understanding of neuroendocrine-related AMPH effects as a function of social and environmental risk factors during adolescence, might deepen our knowledge on the neurobiological bases of genetically determined neuropsichiatric disorders and possibly improve the therapeutical efficacy of psychostimulant drugs.
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PMID:Peculiar response of adolescent mice to acute and chronic stress and to amphetamine: evidence of sex differences. 1186 27


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