Cognitive impairment in schizophrenic patients on event-related potentials component P300

There have been many reports on the Event-Related Potentials (ERPs) abnormalities, especially P300 amplitudes reduction, in schizophrenic patients. However the relationships between P300 abnormalities and schizophrenic subtypes have not been clarified. This study aims to investigate the relationships in a relatively large number of drug free schizophrenics. Seventy three unmedicated schizophrenic patients (45 males, 28 females) who met the DSM-III-R criteria for schizophrenia were tested. Twenty seven of the schizophrenics were paranoid type according to the DSM-III-R, 23 were undifferentiated, 19 were disorganized, 2 catatonic and 2 residual. Seventy three healthy controls were age and gender matched to the patient group. All the ERPs were recorded during auditory odd ball task. Stimuli consists of 2 kHz and 1 kHz tone bursts, and the respective probabilities of the rare and frequent stimuli were 0.2 and 0.8. They were presented random order. The duration of each stimulus was 90 msec with rise and fall times of 10 msec, and the intensity was approximately 70 dB SPL for all the stimuli. The inter-stimulus intervals were 1.7 +/- 0.1 seconds. The subjects were instructed to count the numbers of rare tones. The scalp EEGs were recorded from Ag-AgCl electrodes at 16 sites that referred to linked earlobes. P300 amplitudes reduction [F (1,144) = 39.33, p < 0.001] and P300 latencies prolongation [F (1,144) = 12.41, p < 0.001] were found in schizophrenic group as a whole. Lower amplitude of P300 was observed at both right and left temporal sites in the subjects with undifferentiated type and disorganized type. Although in the subjects with paranoid type, the reduction was recognized at left temporal region, reduced amplitude was not seen at right temporal site. While no relationships between P300 amplitudes, the score of BPRS and SAPS were detected, in the patient with paranoid type, significant negative correlation between P300 amplitudes and SANS total scores was observed (r = -0.425, p = 0.03) at Pz site. These results were discussed with respect to cognitive impairment of schizophrenia.     

High-density recording and topographic analysis of the auditory oddball event-related potential in patients with schizophrenia

BACKGROUND: Prior research has shown reductions of the N1, N2, and P300 auditory event-related potential (ERP) components in schizophrenic patients. Most studies have shown a greater P300 reduction in left versus right temporal leads in schizophrenic patients. These studies were done with sparse electrode arrays, covering restricted areas of the head, thus providing an incomplete representation of the topographic field distribution. METHODS: We used a 64-channel montage to acquire auditory oddball ERPs from 24 schizophrenic patients and 24 controls subjects. The N1, P2, N2, P300, and N2 difference (N2d) amplitudes and latencies were tested for group and laterality differences. Component topographies were mapped onto a three-dimensional head model to display the group differences. RESULTS: The schizophrenic group showed reduction of the N1 component, perhaps reflecting reduced arousal or vigilance, but no N1 topographic difference. An N2d was not apparent in the schizophrenic patients, perhaps reflecting severe disruption in neural systems of stimulus categorization. In the patients, the P300 was smaller over the left temporal lobe sites than the right. CONCLUSIONS: The increased ERP spatial sampling allowed a more complete representation of the dipolar nature of the P300, which showed field contours consistent with neural sources in the posterior superior temporal plane.     

A spatio-temporal analysis of recognition-related event-related brain potentials

Words correctly recognized as previously studied (i.e. old) elicit greater amounts of positive event-related brain potential (ERP) activity over posterior scalp between 400 and 800 ms than do previously unstudied (i.e. new) words. While investigators have reported that this old/new effect consists of more than one subcomponent, the spatio-temporal parameters of these possible subcomponents, as well as any other patterns of brain activity associated with recognition, remain incompletely specified. Thus, ERPs were recorded from 32 scalp sites while 13 subjects performed four repetitions of a study-test recognition paradigm. The subjects' task was to decide whether each word was old or new and press the appropriate button as quickly as possible. The timing and topography of the ERPs elicited by old and new words was assessed with topographic profile comparisons on the areas with a variety of temporal windows, and visualized with potential and CSD maps. The results revealed that seven patterns of ERP activity, dissociable on the basis of their topography, timing and response to experimental variables, were elicited between 300 and 2000 ms. Three of these appeared as subcomponents of the old/new effect (maximal over left medial frontal, left parietal-occipital and right central-frontal scalp), another was related to decision confidence and/or memory trace strength (maximal over left central scalp) and three others appeared to be related to more general aspects of recognition (maximal over the frontal poles, midline frontal scalp and right frontal scalp). Taken together, the seven distinct patterns of neural generator activity described here support the hypothesis that retrieval of information from episodic memory depends on a collection of different processes that occur in a temporally and spatially distributed neural circuit.     

Exposure of nonmigratory pigeons to mancozeb: a sentinel model for humans

Pathologically asymmetrical P300 fields with right lateralized peaks were described in core schizophrenia as an expression of left-temporal functional deficits, while higher than normal amplitudes were found in cycloid psychosis. This latter finding appeared to be specific for cycloid psychosis and was explained by a generalized cerebral hyperarousal. Based on some psychopathological analogies with cycloid psychosis, and on the comparable pharmacological treatment of the acute episodes, a group of 19 manic patients was investigated immediately after remission and clinical stabilization of an episode. Patients with psychotic features were excluded to avoid overlaps with cycloid psychosis. Patients showed normal P300 amplitudes and no pathological asymmetries of the field, but more posterior positive areas compared to age- and sex-matched controls. This indicates that the neurophysiological changes underlying mania are different from both core schizophrenia and cycloid psychosis. Based on previous three-dimensional source location studies, this finding indicates that disinhibition due to reduced frontal lobe activity, and not hyperarousal, is the basic functional mechanism of manic disorders.     

Perigastric lymph node status as a prognostic indicator in patients with gastric cancer

OBJECTIVE: The mismatch negativity, a negative component in the auditory event-related potential, is thought to index automatic processes involved in sensory or echoic memory. The authors' goal in this study was to examine the topography of auditory mismatch negativity in schizophrenia with a high-density, 64-channel recording montage. METHOD: Mismatch negativity topography was evaluated in 23 right-handed male patients with schizophrenia who were receiving medication and in 23 nonschizophrenic comparison subjects who were matched in age, handedness, and parental socioeconomic status. The Positive and Negative Syndrome Scale was used to measure psychiatric symptoms. RESULTS: Mismatch negativity amplitude was reduced in the patients with schizophrenia. They showed a greater left-less-than-right asymmetry than comparison subjects at homotopic electrode pairs near the parietotemporal junction. There were correlations between mismatch negativity amplitude and hallucinations at left frontal electrodes and between mismatch negativity amplitude and passive-apathetic social withdrawal at left and right frontal electrodes. CONCLUSIONS: Mismatch negativity was reduced in schizophrenia, especially in the left hemisphere. This finding is consistent with abnormalities of primary or adjacent auditory cortex involved in auditory sensory or echoic memory.     

The etiologic heterogeneity of schizophrenia

Evidence is increasing in support of the etiologic heterogeneity of schizophrenia. Five distinct diseases/disorders are suggested in this paper, and the relevant studies are reviewed. Familial forms of the disorder include a dopamine psychosis (supported by research documenting both altered dopamine activity and early neuroleptic response among some schizophrenic patients), a neurodegenerative psychosis (supported by investigations that document ongoing change in ventricular brain ratio, elevation of products of cell membrane catabolism within the central nervous system, and age-progressive third ventricle enlargement accompanied by delayed response to neuroleptics), and a neurodevelopmental psychosis (supported by evidence of static enlarged ventricles in some schizophrenic patients and neurological soft signs in high-risk offspring of schizophrenic individuals). Nonfamilial forms include a neurodevelopmental psychosis (supported by evidence of neurodevelopmental abnormalities triggered by neurotropic viruses, radiation, or anoxia) and a lithium-responsive psychosis (supported by evidence of a subgroup of psychotic patients who have low risk of either psychosis or mania in their pedigrees and respond to lithium).     

Inhibitory effects of oleic and docosahexaenoic acids on lung metastasis by colon-carcinoma-26 cells are associated with reduced matrix metalloproteinase-2 and -9 activities

Structural and functional neuroimaging techniques have consistently demonstrated that abnormal lateralization of temporal lobes may be important in identifying the pathophysiologic processes in schizophrenia. The exact nature of these reported abnormalities has not been consistent. METHODS: We examined temporal lobe perfusion using HMPAO-SPECT in 22 individuals with schizophrenia in an effort to establish whether temporal lobe perfusion asymmetry is seen in these individuals, as compared to a group of 22 age- and sex-matched controls. RESULTS: We found that the asymmetry index, a measure of perfusion differences between two homologous compared areas, was lower (more negative) in schizophrenic individuals. The asymmetry indices of patients considered with the results from globally corrected ROI means indicated that the left temporal lobes of individuals with schizophrenia were significantly hypoperfused when compared to controls. This finding does not appear to be caused by medication effects, demographic variables, handedness, imaging artifacts or analysis techniques. CONCLUSION: In our sample, patients with schizophrenia appear to have significant left hypoperfusion relative to right of their temporal lobes. Abnormal lateralization of temporal lobe blood flow may have important clinical implications by assisting with diagnosis and appropriate treatment for individuals with schizophrenia.     

Superior temporal gyrus and the course of early schizophrenia: progressive, static, or reversible?

Accumulating evidence suggests alterations in brain structure, especially in the prefrontal and temporal cortex, in schizophrenia. Previous studies examining the progression of brain structural alterations in schizophrenia have led to conflicting results. Morphometric studies of the superior temporal gyrus (STG) volumes were conducted in a series of neuroleptic-naive first-episode schizophrenic patients, non-schizophrenic first-episode psychotic patients, and matched healthy controls. Three-dimensional MRI scans were carried out in these subjects before and after one year of treatment. Volume reductions were seen at baseline in the left superior temporal gyrus (adjusted for intracranial volume) in both of the patient groups. Pretreatment illness duration was inversely related to the volume of the left superior temporal gyrus; this relation was confined to males. One-year follow-up MRI investigations in a smaller subset of patients suggested that the STG volume reductions may be reversible. No significant changes were noted in the STG volumes in matched healthy controls who were also scanned at baseline as well as at one-year follow-up. These findings have implications for understanding the nature of the neuropathological processes in early schizophrenia, as well as the potential impact of early treatment.     

Visceral afferent stimulation-evoked changes in the release of peptides into the parabrachial nucleus in vivo

OBJECTIVE: Although there is evidence from postmortem studies suggestive of deficient inhibitory neurotransmission of gamma-aminobutyric acid (GABA) in schizophrenia, no direct in vivo evidence has been obtained to date. The authors used single photon emission computed tomography (SPECT) with iodine-123-labeled iomazenil ([123I]iomazenil), a radioligand that selectively binds with high affinity to the benzodiazepine subunit of the GABAA receptor complex in the human brain, to investigate the presence of benzodiazepine receptor abnormalities in the cerebral cortex of living subjects with schizophrenia. METHOD: Dynamic [123I]iomazenil SPECT was performed in 15 patients (14 patients with DSM-III-R schizophrenia and one with schizophreniform disorder) and 12 healthy subjects over a period of 2 hours. The time-integral method was used to generate ratios of "specific" to "nonspecific" [123I]iomazenil binding at equilibrium for several cortical regions. RESULTS: No overall between-group differences in benzodiazepine receptor binding were found, but significant correlations emerged between the severity of schizophrenic symptoms and [123I]iomazenil binding in limbic cortical regions: positive symptom scores were negatively correlated with benzodiazepine receptor binding in the left medial temporal region, and negative symptoms were inversely related to receptor binding in the medial frontal region. These correlations were not significant when a Bonferroni correction for multiple comparisons was applied. CONCLUSIONS: These preliminary results are consistent with previous research implicating limbic cortical regions in the pathophysiology of schizophrenia, suggesting that reduced inhibitory GABAergic tone in these areas may contribute to the appearance of schizophrenic symptoms.     

A developmental study of the effect of temporal order on the ERPs elicited by novel environmental sounds

Event-related brain potentials (ERPs) were recorded from 16 subjects in each of the following age groups, 5-7, 9-11, 14-16, and 20-28 years of age. Subjects performed a novelty oddball task, in which frequent, standard tones (80% probability) were intermixed with infrequent tones to which the subject responded (10%), along with 48 unique novel, environmental sounds (10%). Analyses focused on the effects of temporal order (either serial order within the block or block number) in interaction with age group on the ERPs to the novel sounds. The amplitude and scalp distribution of two ERP components were analyzed, the 'novelty P3,' assumed to reflect aspects of the orienting response, and the P32, a component that may be synonymous with the P3b. Evidence suggests that the frontal aspect of the scalp distribution of the novelty P3 depends upon the integrity of the prefrontal cortex. Temporal order produced systematic (primarily linear) reductions in novelty P3 amplitude that were greater at frontal than posterior electrode sites. The P3(2) did not show consistent effects of temporal order. Both of these phenomena were highly similar for all four age groups. It is concluded that the brain's response to novelty is similar across a wide age range, involving a neural circuit with both frontal and posterior elements.     

Cloning and analysis of a cDNA encoding the BALB/c murine erythrocyte band 7 integral membrane protein

Phospholipid metabolism abnormalities have been suggested by a number of postmortem brain and red blood cell studies in schizophrenia. 31P magnetic resonance spectroscopy enables the examination of phospholipid metabolism in living patients. These in vivo studies have demonstrated that schizophrenic patients have lower prefrontal levels of phosphomonoesters and higher levels of phosphodiesters compared to matched controls. Patients with psychotic depression also seem to show lower levels of phosphomonoesters compared to controls. This suggests that membrane phospholipid differences may not be specific to schizophrenia. Preliminary 31P magnetic resonance spectroscopy studies at high field strength on postmortem temporal lobe samples show no differences between treated schizophrenic patients and controls for phosphoethanolamine and phosphocholine which are the main constituents of the phosphomonoester peak. Further studies are underway in the prefrontal region. While 31P magnetic resonance spectroscopy studies have demonstrated membrane phospholipid abnormalities in schizophrenia, it is not clear whether these findings are specific to schizophrenia or part of a generalized membrane phospholipid abnormality.     

In experimental diabetes the decrease in the eye of lens carnitine levels is an early important and selective event

The relationship between a history of substance use disorder and the early course of psychotic illness was examined in 96 subjects with schizophrenia and 106 subjects with affective psychosis followed in the Suffolk County Mental Health Project, a longitudinal study of first-admission psychosis. Subjects received a structured diagnostic interview and clinical ratings at baseline assessment and again 6 months later. The 6-month assessment included information about treatment received during the interval. A lifetime history of substance use disorder was associated with worse clinical functioning at 6 months for schizophrenia subjects, but not for those with affective psychosis. There were no significant associations of substance use disorder with type of treatment during the interval or with self-reported compliance with medication. Schizophrenia subjects were more likely than subjects with affective psychosis to report cannabis use during the interval and to meet criteria for cannabis use disorder.     

Nutritional status and serum lipids of a rural population in Northeast Thailand--an example of health transition

The authors retrospectively evaluated the etiology and clinical findings of patients with first manifestations of psychotic symptoms after the age of 65. Nearly 10% of over 1,700 consecutive geriatric patients admitted to an acute inpatient psychogeriatric unit had late-life onset psychotic symptoms. About three-fourths of these were women, usually in their seventies. Dementia of the Alzheimer's type was the most common cause of psychosis arising in late life, followed by major depression, medical/toxic causes, delirium, bipolar disorder, delusional disorder, schizophrenia, and schizoaffective disorder. Clinical manifestations consisted mostly of delusions and hallucinations.     

Decreased left frontal lobe N-acetylaspartate in schizophrenia

OBJECTIVE: The authors measured N-acetylaspartate (a putative neuronal marker), using in vivo proton magnetic resonance spectroscopic imaging (1H-MRSI), in the frontal lobes of schizophrenic patients and normal subjects. METHOD: Frontal lobe 1H-MRSI was performed bilaterally on 24 medicated schizophrenic patients and 15 healthy comparison subjects. Levels of N-acetylaspartate, creatine, and choline were determined. RESULTS: Relative to the comparison group, the patients with schizophrenia demonstrated significantly lower levels of N-acetylaspartate in the left frontal lobe. There was no association between level of N-acetylaspartate and duration of illness or medication dosage. No differences between groups or lateralized asymmetries in choline or creatine were noted. CONCLUSIONS: This preliminary study provides support for decreased N-acetylaspartate in the left frontal lobe in schizophrenia and neuronal dysfunction in this brain region.     

Symptom dimensions and brain morphology in schizophrenia and related psychotic disorders

The heterogeneity of symptoms in schizophrenia may reflect heterogeneity of underlying pathophysiological mechanisms. Factor analytic studies have consistently identified three symptom factors, psychotic, negative and disorganized, as independent dimensions of schizophrenic psychopathology. This study examined the relationship of these symptom dimensions with volumes of specific brain regions. One-hundred and sixty-six schizophrenia spectrum patients were clinically evaluated with the Comprehensive Assessment of Symptoms and History (CASH) and scanned with a 1.5 Tesla magnetic resonance imaging scanner. Regions of interest (ROIs) were manually traced on 5 mm and 3 mm coronal slices by a single technician, blind to all aspects of subject identity. Correlations between ROI volumes and indices of symptom severity were determined. Analyses of covariance were then used to test for specific relationships between each of the three symptom dimensions and ROI volumes. Tests were made of each dimension, controlling for all others. Overall symptom severity was significantly correlated with larger ventricle volumes (lateral, third and temporal horns) and smaller temporal lobe, hippocampal and superior temporal gyral volumes. Both psychotic and negative symptom severity predicted increased third ventricular volume. Psychotic symptom severity uniquely predicted decreased superior temporal gyral volume as well as increased temporal horn volume. Within the psychotic symptom dimension, hallucinations alone predicted left superior temporal gyral volume. No significant associations between disorganized symptoms and any ROIs were demonstrated. These results provide clues to the localization of specific brain regions underlying symptom clusters in schizophrenia, and provide further validating evidence for the construct of independent dimensions of psychopathology within schizophrenia and related psychotic disorders.     

Analysis of CAG/CTG repeat size in Chinese subjects with schizophrenia and bipolar affective disorder using the repeat expansion detection method

BACKGROUND: Family studies of schizophrenia and bipolar affective disorder provide evidence for genetic anticipation, which (in common with a number of mendelian disorders), may be caused by triplet repeat expansion. This hypothesis is strengthened by evidence from repeat expansion detection (RED) analysis revealing association between the psychoses and long CAG/CTG trinucleotide repeats. METHODS: We performed RED on Han Chinese subjects with schizophrenia (82), bipolar affective disorder (43), and normal controls (61), using a CTG10 oligonucleotide. RESULTS: Comparison between cases and controls revealed no significant association between long repeats and affected status. We also found no detectable association with age at onset and repeat length in either bipolar affective disorder or schizophrenia. Overall, the size distribution of CAG/CTG repeats in Chinese subjects was not significantly different from those reported previously for Caucasian subjects. CONCLUSIONS: These findings indicate that CAG/CTG repeat expansion is not likely to be a major etiological factor for psychosis in Chinese populations.     

Bipolar affective disorder minus left prefrontal cortex equals schizophrenia

BACKGROUND: An investigation of the relationship between bipolar affective disorder and schizophrenia, following a severe head injury and removal of the left prefrontal cortex. METHOD: A single case report. RESULTS: An individual with past history of bipolar affective disorder suffered traumatic damages to the left prefrontal cortex with a second lesion in the left temporal lobe. The patient developed typical schizophrenia nine months later. The relevance of his brain lesions in determining the schizophrenic symptoms is discussed. CONCLUSION: We propose that the specific pattern of brain injury in this patient was sufficient to change the phenotype from bipolar affective disorder to schizophrenia.     

Movement abnormalities and the progression of prodromal symptomatology in adolescents at risk for psychotic disorders.

The link between movement abnormalities and psychotic disorders is presumed to reflect common neural mechanisms that influence both motor functions and vulnerability to psychosis. The prodromal period leading to psychotic disorders represents both a viable point for intervention and a developmental period that, if studied, could shed light on etiology; however, no published studies have examined the temporal progression of this link. A group with high levels of prodromal symptomatology (i.e., adolescents with schizotypal personality disorder [SPD]; n = 42) and both psychiatric controls (with other personality disorders or conduct disorder [OD]; n = 30) and nonpsychiatric controls ([NC]; n = 49) were recruited. Videotapes of structured psychiatric interviews were coded for movement abnormalities by raters blind to participants' diagnostic status, and follow-up assessments were conducted 1 year later. Controlling for psychotropic medications, the authors found that adolescents with SPD exhibited significantly more motor abnormalities in the face and upper body than did OD and NC controls. At baseline, movement abnormalities were positively correlated with the severity of positive, negative, and total prodromal symptoms. Within the SPD group, baseline movement abnormalities predicted symptom severity 1 year later. Movement abnormalities represent an early risk indicator that may be predictive of later symptom severity and potentially of psychosis onset. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The structure of psychosis: latent class analysis of probands from the Roscommon Family Study

BACKGROUND: The nosologic structure of psychotic illness, still influenced as much by historical as empirical perspectives, remains controversial. METHODS: Latent class analysis was applied to detailed symptomatic and outcome assessments of probands (n=343) with broadly defined schizophrenia and affective illness ascertained from a population-based psychiatric registry in Roscommon County, Ireland. First-degree relatives (n=942) were assessed by personal interview and/or review of hospital record. RESULTS: Six classes were found, all of which bore substantial resemblance to current or historical nosologic constructs. In order of decreasing frequency, they were (1) classic schizophrenia, (2) major depression, (3) schizophreniform disorder, (4) bipolar-schizomania, (5) schizodepression, and (6) hebephrenia. These classes differed on many historical and clinical variables not used in the latent class analysis. Compared with relatives of controls, significantly increased rates of major depression were seen in relatives of depressed and schizodepressed probands. Significantly increased rates of bipolar illness were restricted to relatives of bipolar-schizomanic probands. The risks for schizophrenia and schizophrenia spectrum disorders were significantly increased in relatives of all proband classes except major depression. This increase was moderate for bipolar-schizomanic probands, substantial for schizophrenic, schizophreniform, and schizodepressed probands, and marked for hebephrenic probands. CONCLUSIONS: These results suggest a relatively complex typology of psychotic syndromes consistent neither with a unitary model nor with a Kraepelinian dichotomy. The familial vulnerability to psychosis extends across several syndromes, being most pronounced in those with schizophrenialike symptoms. The familial vulnerability to depressive and manic affective illness is somewhat more specific.