Emotional responding in deficit and non-deficit schizophrenia

Although emotional dysfunction is presumed to be a central part of the deficit syndrome in schizophrenia, it has not yet been empirically investigated in deficit and non-deficit patients. Emotional responding was examined in 19 male deficit patients, 22 non-deficit patients, and 20 non-patient controls. Patients participated in a semi-structured clinical interview that included questions from the Schedule for the Deficit Syndrome (SDS) and the Brief Psychiatric Rating Scale (BPRS), and then were then categorized into deficit and non-deficit groups. In addition, all participants viewed emotional films while their facial expressions were videotaped and then completed self-reports of emotional experience following each film. As predicted, deficit patients were less expressive than non-deficit patients and controls across the films. Contrary to prediction, deficit patients did not report experiencing less emotion to the films than non-deficit patients or controls. Thus, a disjunction in emotional responding appeared to characterize deficit patients, who were less expressive than controls but did not report less emotional experience. Alternative explanations for the findings are considered as are directions for future research.     

Neuropsychological impairment in deficit vs. non-deficit schizophrenia

This study aimed to assess the severity and specificity of cognitive impairments that affect individuals with deficit versus non-deficit schizophrenia. We compared 26 patients with the deficit subtype of schizophrenia (SZ-D) and 79 with non-deficit schizophrenia (SZ-ND) to 316 healthy adults (NC). All study participants completed a battery with 19 individual cognitive measures. After adjusting their test performance for age, sex, race, education and estimated premorbid IQ, we derived regression-based T-scores for each measure and the six derived cognitive domains including attention, psychomotor speed, executive function, verbal fluency, visual memory, and verbal memory. Multivariate analyses of variance revealed significant group effects for every individual measure and domain of cognitive functioning (all ps<0.001). Post hoc comparisons revealed that patients with SZ-D performed significantly worse than NCs in every cognitive domain. They also produced lower scores than the SZ-ND group in every domain, but only the difference for verbal fluency reached statistical significance. The correlations of the effect sizes shown by the SZ-D and SZ-ND patients were of intermediate magnitude for the individual tests (r=0.56, p<0.01) and higher, but not statistically significant for the cognitive domains (r=0.79, p=0.06). Patients with SZ-D demonstrate cognitive deficits that are both common and distinct from those shown by patients with SZ-ND. Their impairment of verbal fluency is consistent with the observation that poverty of speech is a clinically significant feature of patients with SZ-D.     

Saccadic eye movements in essential blepharospasm

Summary To provide evidence of an organic pathology for essential (idiopathic) blepharospasm, reflex saccadic eye movements in response to randomly stepped visual targets were assessed in seven affected patients and seven age-matched controls using the magnetic scleral search coil technique. The results indicate a significant prolongation in latency and a reduction in gain of horizontal saccades, and an increase in latency and reduction of peak velocity of large downward saccades. These findings suggest an organic component to the aetiology of blepharospasm, the pathology of which also appears to involve the oculomotor system. The pattern of the oculomotor disorder does not allow specific localisation but is consistent with the underlying pathology being localised in the basal ganglia.     

Saccadic eye movements and endogenous psychoses

Saccadic eye movements were examined in different psychiatric patient groups. It was found that patients with schizophrenic and schizoaffective psychoses showed significantly increased incidence of dysmetric saccades (dysmetria) as compared to manic-depressive and alcoholic patients as well as healthy controls. However, increased non-fixations (deviations of the gaze from the target point) occurred in all psychotic inpatients but not in alcoholics and schizophrenic outpatients. Significantly increased saccadic reaction times could be found in chronic schizophrenic inpatients only. Furthermore it could be shown in the latter group that the increased dysmetria remains intraindividually relatively constant, in contrast to the other parameters. The results are interpreted as the expression of an impairment of attention of psychotic inpatients, while the dysmetria could represent the equivalent of a disturbed attention typical for psychoses with schizophrenic features.     

Saccadic eye movements in schizophrenic patients

The nature of saccadic abnormalities in schizophrenia was investigated in three different paradigms: (1) the visually guided saccade; (2) the antisaccade; and (3) the remembered saccade paradigm. Subjects comprised 14 schizophrenic patients and 14 normal volunteers. Deficits in the schizophrenic group were observed in the antisaccade and remembered saccade tasks, both of which were characterized by increased latency and reduced gain. Moreover, in the antisaccade task, schizophrenic patients showed an increased number of errors compared with control subjects. Saccadic abnormalities in the patients were correlated with impaired performance on the Wisconsin Card Sorting Test. These data suggest that schizophrenic patients have difficulty in inhibiting reflexive saccades and in producing voluntary saccades. The implications of these findings for a prefrontal cortex dysfunction involved in oculomotor control in schizophrenia are discussed.     

Saccadic eye movements in psychotic patients

Schizophrenic and manic-depressive patients executed saccades to target displacements of 2 to 24 degrees. The latencies, velocities, and accuracy of their saccadic eye movements were normal, although patients' saccadic latencies increased more than controls' for stimulus displacements greater than 10 degrees. In contrast to their normal saccadic latencies, patients had significantly slower than normal mean finger-press latencies. The results have implications for the significance of motoric and attentional deficits in the major psychoses.     

Saccadic eye movements in psychiatric patients

Saccadic eye movements were examined in 110 psychiatric patients and 26 controls, evaluating three parameters, the frequency of dysmetric saccades, nonfixation and the saccadic reaction time. Dysmetric saccades (dysmetria) were defined as saccadic reactions undershooting the target, nonfixation was defined as a deviation of the gaze from the target with the target stationary. While the nonfixation score and the saccadic reaction time were slightly increased in most of the psychiatric patient groups as compared to controls, an increase of the dysmetria score was confined to patients with schizophrenic and schizoaffective disorders. Dysmetria is thus interpreted as the expression of a relatively specific impairment of attention in these patients.     

Saccadic eye movements and anti-epileptic drugs

Saccadic eye movements can be used to evaluate different aspects of brain function, and in this article we are concerned with possible applications in relation to anti-epileptic drug treatment. Recent improvements in the technology of measurement have improved the sensitivity and objectivity of the measures. Here we review the neurophysiology of saccades, their classification, their anatomical basis and cortical control, and then published research articles concerned with the influence of anti-epileptic drugs on saccades and their parameters. It seems likely that certain anti-epileptic drugs (especially those acting on ion channels) exert their effect on saccades through ion channels, and this may have relevance to clinical and pharmacogenetic studies.     

精神分裂症家系中患病同胞缺陷型及非缺陷型分布的一致性

目的　探讨精神分裂症患病同胞对缺陷型及非缺陷型在家系中分布的一致性。方法收集 51个精神分裂症家系 1 1 1例患者 ,共 70对患病同胞 ,用Kirkpatrick缺陷综合征量表评定精神分裂症患者的缺陷症状 ,并将其划分为缺陷型及非缺陷型。采用同胞对法分析患病同胞缺陷型及非缺陷亚型的一致性。结果　精神分裂症患病同胞对缺陷型及非缺陷型不符合随机分布 ,差异具有显著性(χ2 =1 2 40 ,ν =1 ,P <0 0 0 1 )。结论　精神分裂症患病同胞中缺陷型及非缺陷型的分布具有家族聚集现象。     

Concordance of deficit and non-deficit subtypes in siblings affected with schizophrenia

Deficit and non-deficit subtypes were examined for their concordance in 83 sibling pairs of 109 schizophrenic patients belonging to 46 multiply affected families. Using a sib-pair method, we have found that the distribution of deficit and non-deficit syndromes in sibling pairs of schizophrenic patients differed significantly from chance expectation. This familial aggregation suggests that the syndrome may be used to define phenotypes for genetic studies.     

Syndromes of schizophrenia and smooth-pursuit eye movement dysfunction

There have been a number of studies on smooth pursuit eye movement (SPEM) dysfunction in schizophrenia. However, the association between SPEM dysfunction and particular clinical symptoms remains unclear. We examined SPEM dysfunction in relation to schizophrenic symptoms using both the positive/negative dichotomy and the three-syndrome model. Subjects included 78 patients with schizophrenia and 60 healthy control subjects. SPEM performance was indexed by root mean square error. Symptom profiles were assessed using the Positive and Negative Syndrome Scale (PANSS), and the three-primary syndromes were identified by factor analysis of PANSS ratings (Psychomotor poverty: deficit negative symptoms; Disorganization: defined primarily by thought disorder; and Reality distortion: hallucinations and delusions). Compared with controls, the schizophrenia group showed significant impairment in global SPEM function. The three-syndrome approach produced more specific findings than the dichotomous model. Of the three syndromes, only the Disorganization dimension showed a significant association with increased global SPEM dysfunction. The specificity of SPEM dysfunction to Disorganization was verified in comparisons among schizophrenia subgroups and the control group. By contrast, the general domains of positive and negative symptoms were both found to be modestly associated with SPEM dysfunction. The separation of positive and negative symptoms that contribute to Disorganization from those that define Reality Distortion and Psychomotor Poverty has revealed significant new associations between SPEM and schizophrenic symptoms. These findings are interpreted in light of the proposal that the Disorganization syndrome is the central form of pathology in schizophrenia.     

A new method for analyzing smooth-pursuit eye movements

The study of ocular movements has been increasingly used to detect subtle pathological modifications, caused by a wide variety of neurological diseases. We have developed a new microcomputer-based method for the analysis of smoothpursuit ocular movements induced by constant velocity targets moving unpredictably at different velocities (including velocity values as high as 100 deg/s). The ocular movements are recorded by an electro-oculographic technique using silversilver chloride electrodes fixed near the inner and outer canthi of both eyes. The signals are amplified by two DC amplifiers after a low-pass filtering (50Hz), sampled at 250 Hz and digitized in a 12-bit form by an analog/digital converter. For each patient's evaluation, a series of 20 sweeps of the target is generated. The data analysis, which is performed automatically by the microcomputer, is based one the calculation of four parameters: average peak eye velocity (APEV); typical target velocity (TTV); percent target matching index after saccade removal (PTMI); typical matching target velocity (TMTV) after saccade removal. APEV is calculated as the average of the peak velocities estimated from the 20 sweeps. The purpose of TTV, which is defined as the value of target velocity at which the percent gain has decreased to slightly more than one third of the maximum percent gain, is to provide an overall index of the rate at which the percent gain decreases as the target velocity increases. PTMI describes the eye performance for each value of target velocity. TMTV, which represents the target velocity at which the PTMI has decreased to approximately 37%, is an overall index of the rate at which the PTMI decreases as the target velocity increases. This parametrization of smooth pursuit has been tested in 28 healthy volunteers and in one patient with a neurological disease. Our results indicate that our method can provide a reliable and quantitative parametrization of smooth pursuit.

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Sommario L'utilizzo di procedure di analisi computerizzate per lo studio dei movimenti oculari consente di rilevare fini alterazioni patologiche in una ampia gamma di malattie neurologiche. Descriviamo un nuovo metodo di analisi dei movimenti oculari di inseguimento lento. Il segnale, rilevato da ambedue gli occhi con tecnica elettrooculografica, è amplificato da due amplificatori in DC e, dopo un filtraggio analogico a 50 Hz, viene campionato a 250 Hz e digitalizzato. Il movimento di inseguimento lento è elicitato da una mira luminosa che si muove a velocità costante (da 5 a 100 gradi/sec) da un estremo all'altro della barra per 20 volte. L'analisi dei dati, eseguita automaticamente dal calcolatore, è basata sul calcolo di quattro parametri: velocità picco dell'occhio durante il movimento di inseguimento lento (APEV); velocità tipica del target (TTV); indice di matching percentuale della mira dopo la rimozione dei saccadi (PTMI); velocità tipica di matching della mira dopo rimozione dei saccadi (TMTV). L'APEV è costituito dal valore medio della velocità di inseguimento lento dell'occhio quando quest'ultima ha raggiunto il massimo in ciascuna delle varie velocità della mira. Il TTV è definito come il valore della velocità del target in cui il guadagno percentuale dell'APEV è diminuito a circa un terzo rispetto al massimo guadagno percentuale. Questo valore fornisce un indice complessivo che esprime la rapidità con cui il guadagno percentuale dell'APEV diminuisce con l'aumentare della velocità del target. Il PTMI è un parametro che descrive invece la performance globale del movimento di inseguimento lento dell'occhio per ciascuna velocità del target. TMTV rappresenta infine la velocità del target in cui PTMI è diminuita a circa il 37% e costituisce un indice complessivo della rapidità con cui PTMI diminuisce con l'aumentare la velocità di target. Questo tipo di parametrizzazione dei movimenti di inseguimento lento è stata studiata in 28 volontari sani ed in un paziente affetto da una malattia neurologica (demenza di Alzheimer). I risultati indicano che questo metodo di analisi fornisce informazioni che possono essere utili in campo clinico.

     

Plasma nitrate levels in deficit versus non-deficit forms of schizophrenia

OBJECTIVE: To determine whether nitric oxide production levels differ in patients with deficit and non-deficit forms of schizophrenia. METHODS: We investigated plasma nitrate levels, an index of in vivo nitric oxide production, in patients with deficit syndrome (n = 11) and non-deficit syndrome (n = 14) and healthy controls (n = 12) with a combination of high-performance liquid chromatography and the Griess reaction. RESULTS: There was no difference found in mean plasma nitrite levels, but plasma nitrate levels of patients with deficit syndrome were significantly lower than those with non-deficit syndrome (28.0 [SEM 2.5] micromol/L v. 44.2 [SEM 5.5] micromol/L, p < 0.05). CONCLUSIONS: A decline in nitric oxide production may be involved in primary negative symptoms in schizophrenia.     

Effects of ketamine on leading saccades during smooth-pursuit eye movements may implicate cerebellar dysfunction in schizophrenia

OBJECTIVE: Ketamine has proved a useful probe in the study of schizophrenia. Recent studies have shown that ketamine causes abnormalities in eye tracking similar to those seen in patients with schizophrenia. The authors examined the effects of ketamine on leading saccadic eye movements, a specific component of the smooth-pursuit response shown to be abnormal in schizophrenia patients and their relatives. METHOD: Twelve normal healthy volunteers received a 0.1 mg/kg bolus injection of ketamine or placebo in double-blind fashion during a smooth-pursuit eye-movement task. The number of leading saccades and the ratios of leading saccades to smooth-pursuit response time and to total saccadic eye-movement time were measured. RESULTS: Ketamine significantly increased the number of leading saccades and increased the leading saccade ratios for more slowly moving targets. Similar nonsignificant effects were noted at higher target speeds. Ketamine-induced abnormalities were similar to those observed in relatives of schizophrenia patients under drug-free conditions. CONCLUSIONS: These results suggest that neurotransmission mediated by N-methyl-D-aspartate (NMDA) is involved in eye-tracking abnormalities. The generation of disruptive leading saccades during smooth pursuit is thought to be mediated by frontal-thalamic-cerebellar circuitry. Evidence that the locus of this and other ketamine-induced smooth-pursuit eye-movement deficits involves NMDA receptor functioning in the cerebellum is suggested.     

Saccadic eye movements in children with reading disorders

Several reports raised the possibility that dysfunction of saccadic eye movements produces reading disorder (RD), although opposite conclusions have also been reported. In this study, saccadic eye movements were investigated in 13 forth graders with RD and 20 age-matched controls during reading and non-reading tasks. Compared to the control group, children with RD showed significantly higher incidences of both forward and backward saccadic eye movements in reading tasks, while they revealed a significantly lower number of saccadic eye movements in response to sequentially moving targets in two types of non-reading tasks. These problems, seen in non-reading tasks, suggest that excessive saccadic eye movements observed in RD children during reading are not produced by mechanisms involved in the language and phonological processes alone, but also those in the saccadic eye movement process. Dysfunction in the saccadic eye movements could be one of the causal factors that produce RD.     

Reduced left uncinate fasciculus fractional anisotropy in deficit schizophrenia but not in non-deficit schizophrenia

Aims: Schizophrenia is a psychiatric disorder manifesting with heterogeneous symptom clusters and clinical presentations. The deficit syndrome is the condition defined by the existence of primarily negative symptoms, and patients with the deficit syndrome differ from non‐deficit patients on measures of brain structure and function. In the current study, by using diffusion tensor imaging (DTI), we investigated the frontotemporal connectivity that is hypothesized to differ between deficit and non‐deficit schizophrenia. Methods: Twenty‐nine patients and 17 healthy controls were included in the study. The patients had deficit (n = 11) or non‐deficit (n = 18) schizophrenia and they were evaluated clinically with the Schedule for Deficit Syndrome (SDS) and Positive and Negative Syndrome Scale (PANSS). Diffusion‐based images were obtained with a 1.5T Siemens Magnetic Resonance Imaging machine and analyses were carried out with Functional Magnetic Resonance Imaging of the Brain Library Software – Diffusion tool box software. Results: The fractional anisotropy values in the left uncinate fasciculus of schizophrenia patients with the deficit syndrome were lower than those of non‐deficit patients and the controls. There were no differences between non‐deficit schizophrenia patients and controls. Conclusion: These findings provide evidence of left uncinate fasciculus damage resulting in disrupted communication between orbitofrontal prefrontal areas and temporal areas in deficit schizophrenia patients.     

MMPI discriminators of deficit vs. non-deficit recent-onset schizophrenia patients

Seventy-four patients with a recent initial onset of schizophrenia were studied during an inpatient hospitalization for a recent onset of schizophrenia as well as during a 12-month period of outpatient treatment as part of a large longitudinal study at UCLA. The Proxy for the Deficit Syndrome (PDS; Kirkpatrick, B., Buchanan, R.W., Carpenter, W.T., 1993. Case identification and stability of the deficit syndrome of schizophrenia. Psychiatry Research 47, 47-56.) was calculated based on psychiatric symptoms rated on the Brief Psychiatric Rating Scale every 2 weeks throughout the 12 months. The Minnesota Multiphasic Personality Inventory (MMPI) was administered to the schizophrenia patients at the index hospitalization. The 168-item version of the MMPI (MMPI-168) was administered at the baseline point of the 12-month period of outpatient treatment, and again 1 year later. Normal comparison subjects were tested with the MMPI or MMPI-168 at comparable time intervals. The UCLA Social Attainment Scale, a measure of the adequacy of social functioning and relatedness, was examined at the outpatient baseline and 12-month points. During the outpatient period, the Deficit Schizophrenia group (i.e. schizophrenia patients with high 12-month average PDS scores) had lower T-scores than the Non-deficit Schizophrenia group on several MMPI-168 scales, especially scales related to affective distress and anxiety. The MMPI-168 scores of normal subjects were generally the lowest of the three groups, but not always significantly lower than those of the Deficit Schizophrenia group. Social functioning at the end of the 12-month period was worst for the patient group with high deficit (PDS) scores. The findings are congruent with the concept of a Deficit Syndrome for which the PDS is the proxy.     

Discharges of Purkinje cells in monkey's flocculus during smooth-pursuit eye movements and visual stimulus movements

Modulations in discharges of Purkinje cells (P cells) associated with movements of visual patterns were studied in the flocculus of monkeys trained to execute smooth-pursuit eye movements and to suppress optokinetic nystagmus. One class of P cells responded to the movements of visual stimulus regardless of whether the eyes remained stationary (produced retinal-slip velocity) or moved with the stimulus produced eye velocity). These P cells processed high-order information concerning the absolute velocity of stimulus movements and thereby the eye velocity had already been incorporated in the visual responses (visuomotor P cells). The other class of P cells responded to visual inputs resulting from the retinal slip (visual P cells). The majority of visual P cells (82%) also modulated their activities during smooth pursuit. When sinusoidal trackings were executed against a stationary visual background, various types of interactions occurred in the P-cell responses between the converging visual and oculomotor inputs. The type of interaction was related to the preferred direction for the P cell during eye movements and the side of the peripheral receptive field.     

Saccadic and smooth pursuit eye movements in memory-impaired elderly people

The aim of the study was to compare eye movements recorded in 14 non-demented memory impaired elderly subjects with those of 36 sex- and education-matched controls. Eye movements were recorded with the bitemporal electrooculographic technique, and analyzed with a personal computer. Saccades were elicited in accordance with reflexive, predictive and antisaccade paradigms. Smooth pursuit eye movements were elicited with a triangular ramp paradigm. The memory-impaired subjects showed a higher prevalence of increased reflexive saccade latency and a lower smooth pursuit performance index. In addition, we detected a correlation between antisaccade and reflexive saccade latencies. Our results showed very slight differences in eye movement parameters. However, our findings are in keeping with the hypothesis of a subtle involvement of differing cortical areas in memory impaired subjects     

Saccadic eye movements in juvenile variant of Huntington disease

Background and purposeHuntington disease (HD) is a neurodegenerative disease leading to involuntary movements, cognitive and behavior decline. The juvenile variant of HD (JHD) manifests in people younger than 21 and is characterized by a different clinical presentation, i.e. rigidity and bradykinesia. Rapid eye movements were not extensively studied in patients with JHD. Aims of our study were to describe the saccadic eye movements in JHD patients and to find a correlation between the saccade abnormalities, severity of the disease and cognitive and behavior deterioration.Materials and methodsWe studied 10 patients with JHD and 10 healthy subjects. Reflexive and volitional saccades were assessed with the Saccadometer Advanced. The battery of cognitive and behavior tests was performed as well.ResultsWe found a prolonged latency, slowness and decreased velocity of reflexive and voluntary saccades and reduced amplitude of voluntary saccades. Moreover, patients with JHD executed a significantly lower number of volitional saccades and made more incorrect cued saccades than controls. We noted a significant correlation between prolonged latency of reflexive saccades with gap task and disease severity and significant inverse correlation between prolonged latency of reflexive saccades with overlap task, an increased number of incorrect saccades made on a cue and impairment in working memory.ConclusionAbnormalities of saccade eye movements in patients with JHD were similar to those reported in patients with HD. Our findings did not confirm abnormalities previously reported in patients with early onset HD. Abnormal saccade parameters correlated also with a disease severity and cognitive deterioration.