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

Recognition memory was assessed in adult rats that received bilateral injections of saline (sham lesions) or ibotenic acid (lesioned) in the ventral hippocampus as neonates (postnatal day 7, PD7) or young adult (42 days of age, PD42) using the Novel Object Recognition Test (NORT). Normal or sham-lesioned rats were able to distinguish novel from familiar objects over a 0.5 and 2 h delay between the sample and choice phases. Adult rats (PD70) lesioned as neonates performed progressively worse than sham-lesioned animals at delays of 0.5 and 2 h. A single injection of darbepoetin alfa (500 or 5000 U/kg, i.p.), given 1 h before the sample phase restored performance 0.5 or 2 h later in the choice phase to same levels as sham-lesioned rats. Adults lesioned on PD42 displayed deficits in NORT performance with a 2 h delay between the choice and sample phases that were completely reversed by administration of darbepoetin alfa (5000 U/kg, i.p.) 1 h before the sample phase. These results suggest that darbepoetin alfa may have utility in treating memory deficits associated with brain dysfunction related to developmental disorders such as schizophrenia.
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PMID:Darbepoetin alfa (Aranesp) improves recognition memory in adult rats that have sustained bilateral ventral hippocampal lesions as neonates or young adults. 1711 74

The electroencephalogram (EEG) recorded from the human scalp is widely used to study cognitive and brain functions in schizophrenia. Current research efforts are primarily devoted to the assessment of event-related potentials (ERPs) and event-related oscillations (EROs), extracted from the ongoing EEG, in patients with schizophrenia and in clinically unaffected individuals who, due to their family history and current mental status, are at high risk for developing schizophrenia. In this article, we discuss the potential usefulness of ERPs and EROs as genetic vulnerability markers, as pathophysiological markers, and as markers of possible ongoing progressive cognitive and cortical deterioration in schizophrenia. Our main purpose is to illustrate that these neurophysiological measures can offer valuable quantitative biological markers of basic pathophysiological mechanisms and cognitive dysfunctions in schizophrenia, yet they may not be specific to current psychiatry's diagnosis and classification. These biological markers can provide unique information on the nature and extent of cognitive and brain dysfunction in schizophrenia. Moreover, they can be utilized to gain deeper theoretical insights into illness etiology and pathophysiology and may lead to improvements in early detection and more effective and targeted treatment of schizophrenia. We conclude by addressing several key methodological, conceptual, and interpretative issues involved in this research field and by suggesting future research directions.
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PMID:Application of electroencephalography to the study of cognitive and brain functions in schizophrenia. 1736 40

Obsessive-compulsive disorder is a prevalent and clinically significant phenomenon in schizophrenia patients. Both schizophrenia and obsessive-compulsive disorder (OCD) are considered to be neurodevelopmental disorders sharing dysfunctional frontal-subcortical circuitry. Using the Neurological Evaluation Scale (NES), the authors assessed neurological soft signs in 59 patients who met DSM-IV criteria for both schizophrenia and OCD. The two schizophrenia groups (with and without OCD) scored higher than the comparison group but did not significantly differ from one another on any of the NES subscales. The first-episode patients in both groups scored similarly to patients with repeated hospitalizations on all NES subscales. Notably, the OCD patients scored similarly to the two schizophrenia groups on the NES motor sequencing subscale. The author's findings support the notion that neurological soft signs are independent markers of brain dysfunction detectable early in the course of schizophrenia. However, they are of limited value as a putative endophenotype in a search for specific etiological mechanisms underlying a schizo-obsessive subgroup of schizophrenia.
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PMID:Neurological soft signs in schizophrenia patients with obsessive-compulsive disorder. 1743 Oct 60

Dichotic listening (DL) has been used as a tool to investigate possible left cerebral dysfunction in schizophrenia. However, the wide range of DL tests (e.g., words, emotions, sentences) as well as patient groups ("heterogeneity") has introduced several confounders. Assessing relatives of patients with schizophrenia may overcome some of these problems, and may be more useful in determining if loss of functional cerebral laterality in schizophrenia is a state or a trait phenomenon. The fused consonant-vowel DL test was administered to 114 subjects: 20 individuals with familial schizophrenia, 42 of their healthy relatives, and 52 healthy volunteers. We did this to investigate whether the normal language processing asymmetry-a right ear advantage (REA)-is present, and whether it could serve as a marker for genetic liability. General performance accuracy level was lower in schizophrenia patients and their relatives but the expected REA was present in all groups. Adjusting for age, accuracy, and obligate status made no difference. In conclusion, familial schizophrenic patients and their relatives have normal REA and hearing laterality on the fused DL test.
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PMID:Evidence of normal hearing laterality in familial schizophrenic patients and their relatives. 1772 25

Kraepelin's dichotomy, manic-depressive insanity and dementia praecox, are contrasting and true endogenous disease entities which affect excitability, the fundamental property of the CNS. Kraepelin wanted to establish a valid classification and hit the extremes in brain structure and function at a time when we had no knowledge of brain dysfunction in "functional" psychoses. The aetiology is now known: the psychoses are part of human growth and maturation and might be classified according to their brain dysfunction, which is exactly what Kraepelin wanted. However, presumably to reduce the stigma attached to the word "psychosis", there is currently a strong initiative to eliminate the concept. But knowledge of what is happening in the brain in a psychosis might be more helpful in reducing stigma. It is suggested that psychosis is due to an affection of the supplementary motor area (SMA), located at the centre of the Medial Frontal Lobe network. The SMA is one of the rare universally connected areas of the brain, as should be the case for such a key structure that makes decisions as to the right moment for action. This important network, which partly has continuous neurogenesis, has sufficiently widespread connections. The SMA, a premotor area located on the medial side of the frontal lobes, is one of the last regions to reach a concurrence of synaptogenesis. An affection of the SMA, a deficient or abolished Delayed Response Task, seriously disturbs our relation and adaptation to the surroundings. We usually master the Delayed Response Task around the age of 7 months, a time at which the second CNS regressive event takes place, which proceeds from the posterior to the anterior of the brain. In very late maturation, a persistent affection of the SMA might occur. We experience a chronic psychosis: infantile autism (IA), a chronic inability to act consciously, which contrasts with the episodic SMA affection post-puberty, when excitation is reduced due to excessive pruning of excitatory synapses. Silent spots are the result of insufficient fill-in mechanisms following a breakdown of circuitry. They may affect the SMA in the case of very late puberty. An acute reduction in excitation and concomitantly a marked increase in silent spots might lead to an acute psychosis. A frontal preference is likely, given that a reduction might occur anywhere in the cortex, but particularly in the areas maturing latest. The varying localisations probably explain the difficulty in accepting schizophrenia as a disease entity. The multifactorial inheritance of the dichotomy implies that the genetics are not fate, a psychotic development might be prevented given enough epigenetic factors: brain food (omega 3). Might the present dietary adversity, with its lack of brain food, be responsible for a rising incidence in psychosis? A psychosis is an understandable and preventable dysfunction of the brain, and its mechanisms are known. Primarily a disorder of reduced excitation in an attenuated CNS, this explains why all the neuroleptics are convulsants, raising excitation, in contrast to all antidepressives, which are anti-epileptic.
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PMID:What is a psychosis and where is it located? 1851 23

To evaluate whether nystagmus has clinical significance in psychiatric patients who have functional and/or organic brain dysfunction. We performed gaze, positional and positioning nystagmus tests on 227 patients with psychiatric diseases (144 men, 83 women, with an average age +/- SD of 62.5 +/- 14.0 years) in order to evaluate the frequency and characteristics of nystagmus. Patients were classified according to the underlying disease. Normal control subjects were 107 subjects (26 men, 81 women, with an average age +/- SD of 35.6 +/- 10.0 years). Nystagmus was observed in 56 (24.7%) of 227 cases. Nystagmus was seen in 16 (59.3%) of 27 cases of alcoholism, 14 (22.2%) of 63 cases of organic psychiatric disorders, 25 (20.2%) of 124 cases of schizophrenia, 1 (20.0%) of 5 cases of excited mental retardation, 0 (0.0%) of 7 cases of mood disorders, 0 (0.0%) of 1 case of anxiety disorders and 1 (0.9%) of 107 subjects of normal control. There was a significant difference between psychiatric diseases and normal control. These results indicate that nystagmus may also be a very important clinical finding not only in patients with neurological and neuro-otological diseases, but also in patients with psychiatric diseases.
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PMID:Nystagmus using video-oculography in psychiatric patients. 1900 80

Schizophrenia is a major mental disorder that affects approximately 1% of the population worldwide. Cognitive deficits are a key feature of schizophrenia and a primary cause of long-term disability. Current neurophysiological models of schizophrenia focus on distributed brain dysfunction with bottom-up as well as top-down components. Bottom-up deficits in cognitive processing are driven by impairments in basic perceptual processes that localize to primary sensory brain regions. Within the auditory system, deficits are apparent in elemental sensory processing, such as tone matching following brief delay. Such deficits lead to impairments in higher-order processes such as phonological processing and auditory emotion recognition. Within the visual system, deficits are apparent in functioning of the magnocellular visual pathway, leading to higher-order deficits in processes such as perceptual closure, object recognition, and reading. In both auditory and visual systems, patterns of deficit are consistent with underlying impairment of brain N-methyl-d-aspartate receptor systems.
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PMID:When doors of perception close: bottom-up models of disrupted cognition in schizophrenia. 1932 31

Schizophrenia is a brain disease with differing symptomatic presentations, outcomes, and complex genetic mechanisms. A selection of recent work integrating clinical observations, human brain imaging and genetics will be reviewed. While the mechanics of brain dysfunction in schizophrenia remains to be well understood, the emerging evidence suggests that a number of interacting genetic mechanisms in dopaminergic and glutamatergic systems affect fundamental disease-related cognitive brain processes and may do so early in disease neurodevelopment. The availability of new imaging and genetic technologies, and institutional support for research in the translational neurosciences, extends the hope that increased understanding of these brain processes could yield meaningful clinical applications.
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PMID:Cognitive dysfunction in schizophrenia: a perspective from the clinic to genetic brain mechanisms. 1952 42

Schizophrenia has complex genetic heritability. It is also genetically heterogeneous. To the extent that genes are associated with symptom constellations in schizophrenia, they do so by affecting the development and function of neural systems that mediate the expression of such diverse behavioral, cognitive and perceptual phenomena. The genetic mechanisms of human brain dysfunction remain to be well understood. "Imaging genetics" is an emerging field that attempts to integrate the basic biology of putative disease mechanisms with physiological correlates from the live human brain. Here, we review recent imaging genetics work on prefrontal brain systems associated with working memory and executive function - heritable traits relevant to schizophrenia. Starting with genetic variation in dopaminergic systems (e.g., COMT), we examined the modulation of prefrontal brain networks during active cognitive processing; there is also evidence that variation in the expression of dopamine-related downstream intra-cellular signaling molecules (e.g., AKT1) are implicated. Moreover, these genetic variants evidence epistasis on neuroimaging measures, lending further support to the conceptualization that non-additive combinations of multiple genes modulate active human cognitive brain mechanisms. The imaging genetics platform therefore could extend understanding of genetic mechanisms of human cognitive brain processes relevant to neuropsychiatric disease.
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PMID:Prefrontal cognitive systems in schizophrenia: towards human genetic brain mechanisms. 1963 31

Considerable progress has been achieved over the past 15 years in uncovering the biological basis of major psychiatric disorders. Since psychopharmacological treatment is thought to act on the underlying biological basis of the disease, brain imaging techniques enable us to understand the mechanism of action of such compounds. One important tool used to determine patterns of brain dysfunction and how psychopharmacological agents such as antipsychotic compounds work is single-photon emission computerised tomography (SPECT). This technique allows determination of striatal D(2) receptor occupancy rates, which are associated with the extrapyramidal side effects (EPS) of antipsychotic drugs. Studies have confirmed that atypical antipsychotic agents have lower occupancy rates than typical agents. No association has been found between D(2) receptor occupancy rates in the striatum and antipsychotic efficacy, and it therefore appears that striatal D(2) receptor occupancy rates are not necessary for the antipsychotic effect of such agents in schizophrenia. The availability of more refined radioligands will help us not only to understand the action of antipsychotics but also the pathophysiology of schizophrenia.
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PMID:IBZM-SPECT imaging of dopamine D(2) receptors with typical and atypical antipsychotics. 1969 68


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