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

After John Warnock Hinckley jr. had fired shots at President Reagan and had severely injured three others, he was considered not guilty by reason of insanity and brought to a psychiatric hospital. The case caused an unprecedented public interest because the psychiatric testimonies were contradictory (schizophrenia vs. personality disorder). According to the known facts it is very unlikely that a German psychiatrist would have diagnosed Hinckley as schizophrenic. One of the sequels of the sentence was a lowering of the reputation of psychiatrists for their inability to arrive at clear diagnosis. Another sequel was to increase the funds for research in biological psychiatry. Still another sequel was an insanity defense reform bill. The scientific debate and public discussions continue.
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PMID:[The Hinckley case and some sequelae for psychiatry]. 226 96

Smooth pursuit eye movements (SPEMs) have been consistently found to be abnormal in the majority of schizophrenic patients. The traditional SPEM measurement technique, however, fails to inform us about the underlying oculomotor deficit in these patients, since it remains a non-specific and a global oculomotor measure. A number of diverse clinical features such as tardive dyskinesia (TD) or negative symptoms correlate with the SPEM abnormality. Other eye movement abnormalities such as fixation difficulties, increased "volitional" saccadic latency and saccadic distractibility in anti-saccade paradigm have also been noted in schizophrenic patients. Still, it remains unclear how these different eye movement measures relate with each other and with the traditional SPEM measure, the presence of which is so widely described in schizophrenia. The advantage of some newer oculomotor paradigms is their functional specificity and the degree to which their biology is known. To further address these issues and to search for clinical correlates of various eye movement abnormalities found in schizophrenia, we have developed a battery of oculomotor measures to be administered to a large number of clinically well described schizophrenic patients and normal controls. The results from a preliminary analysis of a relatively small number of subjects are presented here, thus limiting the scope of possible conclusions. But, these results do indicate that this technique of studying multiple paradigms for oculomotor control in schizophrenia may prove to be fruitful.
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PMID:Oculomotor abnormalities and their clinical correlates in schizophrenia. 262 22

In the 1950s antipsychotic antidopaminergic drugs were introduced as the pharmacological treatment of schizophrenia. In the last 35 years a large fund of knowledge has been acquired about these drugs. Still, a number of issues regarding them require further addressing. We have reviewed the literature on some of these issues, focusing on those factors that the previous studies have resolved inadequately. The issue of optimal dosages of antipsychotics in schizophrenia has been analyzed from the perspective of the dose requirements during "rapid tranquilization", "in acute psychotic phases of schizophrenia", "in chronically hospitalized psychotic schizophrenic patients" and during "maintenance phases of schizophrenia". We have briefly discussed the different methodologies available for measuring neuroleptic levels in plasma, their methodological weaknesses and strengths and some of the larger studies done with chlorpromazine, haloperidol and fluphenazine to establish correlations between levels, treatment response, oral dosages and side-effects. The theoretically fascinating concept of supersensitivity psychosis has been reviewed and the theoretical and practical weaknesses that exist in most of the papers that have claimed validity for this concept are presented. The article also reviews the preclinical, postmortem and clinical research that demonstrates the presence of site selectivity for dopamine receptors in the newer atypical neuroleptics. Finally, the article briefly reviews the current status of some unorthodox clinical strategies, that may be potentially applicable in managing schizophrenic disorders.
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PMID:Antipsychotic drugs in schizophrenia: current issues. 289 85

Therapy with classical neuroleptics is not effective enough and its adverse effects are quite disabling, especially in chronic or negative schizophrenia; that is probably why adjunctive therapy is so common. Still conclusive evidence concerning the potential benefit of one or another therapeutic association is scarce. Intrinsic heterogeneity of schizophrenias and tremendous methodological problems constitute plausible explanations. Besides studies are usually realised among unselected patients. Available data about adjunctive therapy with anticholinergics, propranolol, antidepressants, benzodiazepines, lithium and carbamazepine are briefly reviewed here.
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PMID:[Associated psychotropic drugs in deficit schizophrenia]. 876 41

The finding by Straub et al. (1995) on 6p22-24 is one of the strongest reports so far in psychiatric genetics. It appears to be substantially replicated by Schwab and collaborators (1995; 1997), and to a lesser extent by Moises et al. (1995). Still, this data does not fulfill the criteria of Lander and Kruglyak (1995) for a confirmed finding in complex disease. There are a number of data sets that do not appear to show linkage. Further genotyping work needs to be done in this area and additional markers in the area would be helpful in the available data sets. It should be noted that the Straub and Kendler dataset (Straub et al., 1995, 1997; Kendler et al., 1996), with 754 affecteds, is substantially larger than any other, and should be weighted concomitant with this. Still, additional data will be necessary before the finding may be firmly accepted. Candidate gene studies have started in this area. The SCA locus is promising on theoretical grounds, but has been only weakly positive in two studies so far. The HLA locus is interesting in relation to autoimmune theories of schizophrenia. There is a long history of HLA studies in schizophrenia with mixed results. HLA is located centromeric to the major positive region identified by Straub, but perhaps not too far to be considered a candidate region. Family-based association studies will be necessary to clarify whether there is a true association in this area. The location identified by Cao et al. (1997) on 6q is promising. Straub and Kendler's data set has been partially tested in this region with negative results. Gejman and co-workers (1997) have recently reported additional positive data in this region from Levinson and Mowry. Additional studies in this area are indicated.
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PMID:Chromosome 6 workshop. 968 28

Many psychiatrist and other mental healthcare professionals consider the availability of atypical antipsychotic drugs a welcome advance in the treatment of schizophrenia. Atypical agents have show to be effective against both positive and negative symptoms of schizophrenia, and in general, their efficacy makes patients more responsive to rehabilitation efforts. Although drugs are a cornerstone of treatment, optimal management of chronic ambulatory outpatients with schizophrenia also depends of psychosocial and other approaches. Still, noncompliance needs to be addressed as schizophrenia patients often fail to take their medications for a variety of reasons, including undesirable side effects and lack of insight or denial of having a mental disorder. A four-vector model for optimal management of chronic ambulatory outpatients includes the biological, psychological, social, and spiritual domains. Although the resources for providing comprehensive, forward-looking management are not universally available in many areas of the United States, clinicians should always strive for the ideal.
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PMID:Chronic ambulatory outpatients and four-vector management. 1018 Oct 73

Fifty years of advances in the pharmacotherapy of major depression (MDE), mania, schizophrenia, and other severe and persistent psychiatric disorders have neither made ECT obsolete nor unnecessary. However, advances in pharmacotherapy have radically changed the practice of ECT. ECT is rarely a first-line treatment of mental disorder, unless the clinical situation is desperate. Otherwise, ECT is most often offered to persons who have failed to respond to pharmacotherapy, thus defining a relatively treatment-refractory population for ECT. The physician who refers patients for ECT, as well as the ECT provider, must be able to judge at what point a patient is deemed "medication resistant", implying expertise in pharmacotherapy for both the referring physician and the ECT provider. Authoritative sources from 20 years ago quoted antidepressant response rates > or = 90% for ECT, but the antidepressant response rate in medication-resistant MDE may be only 60%. Improvements in the safety of ECT have resulted in the referral of large numbers of older persons for ECT. High relapse rates after ECT are perhaps the biggest problem presently facing patients and providers. High relapse rates are not surprising given that (i) most patients are medication resistant, and (ii) ECT is usually withdrawn at the moment it becomes effective. Although continuation/maintenance ECT is an option in preventing relapse, it may not be a practical solution for persons still in their productive years, and it is resource-intensive. Still, continuation/maintenance ECT is the only method to prevent relapse and recurrence of severe psychiatric disorder for some persons.
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PMID:Electroconvulsive therapy in the era of modern psychopharmacology. 1160 37

Schizophrenic patients are known to feature alterations in their cognitive performances, principally in executive functions, attention and memory. In this last domain, studies have shown a relatively severe and global deficit, which can be assessed in chronic and first episode patients. It seems that the memory dysfunction is independent of age and intellectual level, but does correlate with negative psychopathology and global functioning. In the study of memory dysfunction, attentional capacities, information processing and symptomatology have to be considered as determining factors. It has been shown that patients with schizophrenia perform poorly in selective attention tasks and that this deficit may interfere with learning. In the same way, the slowing of information processing contributes to a superficial and incomplete learning. The impact of symptomatology has also to be considered, as negative and depressive symptoms are linked to mnesic performances. The majority of studies bearing on working memory and schizophrenia show an alteration of performances, but studies on long term memory are more equivocal. Procedural memory seems to be preserved, while declarative memory is impaired. These results support the hypothesis that in schizophrenia, memory processes that are consciously controlled are impaired, contrary to implicit learning which may be intact. Nevertheless, studies bearing on semantic memory and episodic memory show controversial results. Still, many authors argue that schizophrenic patients have difficulties in recalling learned material, specially when a delay or a interfering task are introduced in the test. Besides, the schizophrenic subjects do not use the semantic properties of the words, as well as the control subjects, when they have to learn a words list for example. The main goal of the present study was to examine the auditory-verbal learning capacities of 31 schizophrenic patients (20 men and 11 women, 19-56 years old), compared to 27 healthy subjects (11 men and 16 women, 23-56 years old). All subjects received an evaluation including the Rey Auditory-Verbal Learning Test, used to study the progressive acquisition of 15 disyllabic words which are successively orally presented five times to the subject. About forty-five minutes after the last of the five immediate recalls, the delayed recall is assessed and a percentage of retention is also calculated. Visual reasoning and attention capacities were studied with the Progressive Matrix and the d2 encumbrance test respectively. Global psychiatric symptomatology of the patients group was assessed with the Brief Psychiatric Rating Scale. Considering the literature existing on the verbal learning capacities of schizophrenic patients, it was expected that the patients would perform poorly and learn slower than controls. The initial learning of the material, which is a critical stage for schizophrenic patients, was studied with particular attention as well as the effect of the introduction of a delay upon the recall of the words list. A secondary objective of the study was to investigate the role of visual reasoning and attention upon auditory-verbal learning process. According to published studies, it is expected that schizophrenic patients manifest some impairment in the domains of visual reasoning and attention. The question is to know whether it alters performances in the auditory-verbal learning test or not. Finally, the links between clinical characteristics of the patients, like age and illness duration, and their learning performances were explored. Statistical analysis included first a descriptive analysis of data to examine differences between the two groups. Second, ANCOVAs were used in order to control the respective impact of educational level, attention capacities and verbal reasoning capacities upon learning performances. Third, Spearman's correlations were used to detect links between clinical characteristics of the patients and learning performances. The comparisons between patients and controls confirmed that schizophrenic patients scored less in the attentional and visual reasoning tasks. They also featured a lower educational level compared to the healthy subjects. In the auditory-verbal learning test, the patients showed altered performances in the five recalls, as well as in the delayed recall and for the retention percentage. In order to control the impact of educational level, attentional and visual reasoning capacities, these parameters were introduced in the statistical analyses. Educational level did not influence memory alterations in the schizophrenic group. However, attention and, to a lesser extend, visual reasoning had an impact on the comparison of memory scores: when controlling attention, almost no significant group effect remained. Finally, the exploratory analyses of links between clinical characteristics and memory only revealed the presence of a significant negative correlation between illness duration and learning performances. Thus, the analyze of data showed that schizophrenic subjects featured poor performances in the domains of attention, verbal reasoning and auditory-verbal memory. Further analyses taking into account group differences on attention suggest that the impairment featured by schizophrenic patients in the domain of verbal memory strongly relies on an attentional deficit. These results are discussed according to the existing literature and methodological limitations. Clinical implications are also discussed.
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PMID:[Influence of attention on an auditory-verbal learning test in schizophrenic patients]. 1223 38

Despite the fact that most researchers acknowledge the high prevalence of comorbid substance abuse among schizophrenic patients, there is no common agreement regarding the etiology of this serious public health problem. At the center of this debate though, Khantzian's self-medication hypothesis has captured most of the attention. In the present literature review, the authors evaluate this hypothesis in the light of our current knowledge. Formulated in a clinical context, in reaction to the psychoanalytic interpretation of addiction as a pleasure seeking pathology, Khantzian's hypothesis holds that schizophrenic patients use psychoactive substances to relieve their symptoms. Properly understood, this conjecture presupposes that, with the relief of certain target symptoms, substance use would no more be a necessity. But in reality, the use of psychoactive substances usually leads to a general deterioration of the patients' condition. Pharmacodependent schizophrenic patients relapse more often, they are more frequently hospitalized, they show more violent behaviors, and they are more frequently homeless. In particular, the positive symptoms of these patients are generally exacerbated by the psychoactive drugs--with the possible exception of opiates. This observation is in lign with the fact that psychostimulants (cocaine, amphetamines), anesthesic dissociatives (PCP, ketamine) as well as hallucinogens (cannabis, LSD) are all known to exert psychotomimetic effects. As for negative symptoms, the reality is more complex. Preliminary results certainly suggest that stimulants (minor or major) relieve these symptoms, but in the case of the other psychoactive substances, empirical evidence remains fragmentary. Still, the properties of psychoactive substances invite to pay close attention, among the negative symptoms, to the cognitive deficits, the social inaptitudes and the hedonic deficits of these patients. Unsatisfied with the self-medication hypothesis, an increasing number of researchers hypothesize that schizophrenic patients abuse drugs in hope to relieve the negative affects (stress, depression) that commonly accompany their symptomatology. Interestingly, increasing data link these negative manifestations and substance abuse among schizophrenic patients. But these same data do not elucidate whether these manifestations are primary or secondary to drug abuse. For the moment, these findings must be replicated. Furthermore, it remains to be clarified what negative affect is involved here. Is it stress, anxiety or, as commonly thought, depression? Other paths aim in the direction of personality traits and dissociation. The first path is suggested by recent studies demonstrating that pharmacodependent schizophrenic patients differ from non-abusing schizophrenics in that their personality is characterized by traits such as sensation seeking and impulsivity. As for the second path, it is suggested by a recurrent observation in addictive medicine practice, that is: alcohol, cannabis, ketamine, LSD, opiates, PCP, all these substances can induce dissociative states (depersonalization, derealization, etc.). Surprisingly, most of the hypotheses advanced so far have been formulated without reference to neuroscience. However, from a biological perspective, substance abuse among schizophrenic patients appears paradoxical: while the positive symptoms of schizophrenia might involve an hyperactivity of the reward system, the drugs of abuse all seem to increase dopamine release in that same system. That very paradox further casts some doubt on the self-medication hypothesis. And it opens an alternative: schizophrenic patients might be biologically vulnerable to the rewarding effects of drugs abuse. On the therapeutic level finally, the authors argue that polypharmacy medications such as clozapine and quetiapine, known to act on the reward system preferentially to the extrapyramidal system and known to dissociate fastly from the dopamine-D2 receptor, could simplify clinical intervention.
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PMID:[Schizophrenia and addiction: An evaluation of the self-medication hypothesis]. 1287 43

Working memory (WM) deficit in schizophrenic patients has been well established. Still, underlying biological substrate of the impairment is not clear. Among neurotransmitter hypotheses of schizophrenia, N-methyl-D-aspartate (NMDA) receptor model is mostly supported, considering that NMDA receptor antagonist can elicit both psychosis and cognitive impairment observed in schizophrenic patients. In current study, to test the neuropsychological and the electrophysiological effects of NMDA receptor in WM, event-related potentials (ERPs) of Sternberg's short-term memory scanning task (SMST) were analyzed in 10 healthy subjects under intravenous administration of a subanesthetic dose of ketamine (0.65 mg/kg/h) or placebo (normal saline). Late positive component (LPC) of ERP was hypothesized to reflect later stage of WM. Brief Psychiatric Rating Scale score was significantly increased (t=-5.75, df=9, P<.001) and correct response rate was significantly decreased (t=2.21, df=9, P=.054) after ketamine administration. Neither reaction time nor LPC latency, which reflect memory scanning time, was changed. Amplitude of LPC was significantly reduced after ketamine administration (z=-2.31, number of observations=120, P=.021). In conclusion, NMDA receptor antagonist administration elicited WM deficit both in behavioral and electrophysiological level. Electrophysiological component reflecting later stage of WM was impaired by NMDA antagonist.
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PMID:N-methyl-D-aspartate receptor in working memory impairments in schizophrenia: event-related potential study of late stage of working memory process. 1449 16


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