Do self-reports of perceptual anomalies reflect gating deficits in schizophrenia patients?

Jin and colleagues presented an innovative study examining P50 suppression and patients' self-reported perceptual anomalies as two related operational measures of sensory gating deficits in schizophrenia patients. They found that those schizophrenia patients who endorsed experiences of sensory inundation had normal levels of P50 suppression, whereas patients who tended to endorse fewer complaints of perceptual anomalies had P50 suppression deficits. Jin et al's finding challenges the common belief that P50 suppression deficits are associated with cognitive and sensory anomalies reflecting poor gating in schizophrenia patients. This article comments on how the dissociation between phenomenological experiences of gating disturbances and P50 suppression might be explained by the limits of self-report in schizophrenia patients who have deficient insight and self-awareness. We hypothesize that the self-reported inability to screen out irrelevant stimuli reflects a voluntary, controlled process that is different from the involuntary, automatic process measured by P50 suppression.     

Poor premorbid social functioning and theory of mind deficit in schizophrenia: evidence of reduced context processing?

Investigations have demonstrated deficits in theory of mind (ToM) ability in schizophrenia. Yet, the development of, and mechanisms associated with these deficits are not well understood. The present investigation examined the hypothesis that, among chronic schizophrenia patients, impaired ToM is associated with failures in context processing, greater disorganized symptoms, and poor premorbid functioning. Forty-two inpatients with schizophrenia spectrum disorders were assessed on tests of ToM, visual and linguistic context processing, executive functioning, and verbal IQ. Symptomatology and premorbid functioning were also assessed. Results revealed that more impaired ToM was associated with poorer performance on both visual and linguistic context processing measures and higher ratings of disorganization on the BRRS. ToM was also associated with poorer childhood social functioning and an earlier age of illness onset. ToM was not associated with verbal processing speed, verbal fluency, response inhibition, sequence learning, or estimated verbal IQ. A significant regression model including measures of childhood peer problems and visual and language context processing significantly predicted ToM performance and accounted for 43% of the variance. These findings suggest that, among chronic schizophrenia patients, deficits in ToM ability may be the result of context processing impairments. These impairments may be a factor in both poor social functioning during childhood and greater disorganized symptoms after illness onset.     

Looking forward: An impaired ability in patients with schizophrenia?

When two visual stimuli occur within 8 to 17ms of one another, subjects cannot tell they are asynchronous, yet recent results show they are not processed as simultaneous. Two spatially separate squares were presented at an interval ranging from 0 to 92ms and remained on the screen until subjects responded. Subjects pressed a right or left response key according to the judged simultaneity/asynchrony of the stimuli. We evaluated the Simon effect, i.e., the tendency to press the key on the same side as the stimulus. We found an effect even when the squares were displayed on opposite sides of the screen, with their onsets separated by less than 20ms. Controls were biased towards the last stimulus, whereas patients with schizophrenia were biased towards the first. We investigate here whether the results are related to spatial or temporal processing. Using the same paradigm, we explored the impact of spatial grouping by comparing connected vs. unconnected stimuli and manipulating the predictability of the second stimulus location. We tested different groups of mildly symptomatic patients and matched controls in two studies. Under 20ms, when stimuli were connected and the 2nd square location was predictable, patients tended to press the key to the side of the 1st square, whereas controls displayed the opposite tendency. The results suggest that controls put more emphasis on the last occurring event, but not patients with schizophrenia. This impairment is observed when spatial difficulties are removed, suggesting it is related to time rather than space.     

Measurement of insight in patients with bipolar disorder: are self-rated scales developed for patients with schizophrenia applicable?

Our aim was to study if the Birchwood Insight Scale has acceptable psychometric properties when used for patients with bipolar disorders. Patients with schizophrenia (n = 101), bipolar I (n = 57), and bipolar II disorder (n = 37) completed the self-report scale. The items form 3 subscales, awareness of illness, relabeling of symptoms, and need for treatment. The total scale had good internal consistency for patients with schizophrenia, fairly good for bipolar I, but poor for bipolar II disorder. On subscale level the internal consistency was mostly marginal to poor for all patient groups. The level of insight was similar in schizophrenia and bipolar I disorder. The psychometric properties for the insight scale were poorer in bipolar disorders than in schizophrenia, and the scale did not work for patients with bipolar II disorder. This suggests a cautious use of the scale across different diagnostic groups.     

Is lateral bias anomalous in early-onset schizophrenia? Selected comparisons with normal populations

The aim of this study was to investigate lateral bias in patients with early-onset schizophrenia. Hand, eye, and foot preferences and relative hand skill were examined in early-onset patients (n=44) and matched controls (n=39), and were compared with population estimates. Patients demonstrated a significant excess in mixed handedness (20.5% vs. 8.5%) relative to population estimates and reduced relative hand skill on a pegboard task compared with controls. Left eye preference was significantly less common in schizophrenic patients relative to population estimates. Crossed eye-hand and eye-foot preferences were not significantly increased in the patient group as a whole but were present, respectively, in four of nine and five of nine mixed-handed patients but in none of five mixed-handed controls. These findings are consistent with the view that lateralisation is anomalous in schizophrenia early in the course of illness.     

Treating patients with schizophrenia deficit with erythropoietin?

This systematic review summarizes and critically appraises the literature on the effect of erythropoietin (EPO) in schizophrenia patients and the pathophysiological mechanisms that may explain the potential of its use in this disease. EPO is mainly known for its regulatory activity in the synthesis of erythrocytes and is frequently used in treatment of chronic anemia. This cytokine, however, has many other properties, some of which may improve the symptoms of psychiatric illness. The review follows the preferred reporting items for systematic reviews and meta-analysis (PRISMA) statement guidelines. Three databases (Medline, Web of Science, and Cochrane) were searched combining the search terms 'erythropoietin AND (psychotic disorders OR schizophrenia)'. Seventy-eight studies were included in qualitative synthesis, a meta-analytic approach being prohibited. The findings suggest that several EPO cerebral potential properties may be relevant for schizophrenia treatment, such as neurotransmission regulation, neuroprotection, modulation of inflammation, effects on blood-brain barrier permeability, effects on oxidative stress and neurogenesis. Several potentially detrimental side-effects of EPO therapy, such as increased risk of thrombosis, cancer, increased metabolic rate and mean arterial blood pressure leading to cerebral ischemia could severely limit or halt the use of EPO. Overall, because the available data are inconclusive, further efforts in this field are warranted.     

Is gamma band EEG synchronization reduced during auditory driving in schizophrenia patients with auditory verbal hallucinations?

Auditory verbal hallucinations (AVH) in schizophrenia patients assumingly result from a state inadequate activation of the primary auditory system. We tested brain responsiveness to auditory stimulation in healthy controls (n=26), and in schizophrenia patients that frequently (n=18) or never (n=11) experienced AVH. Responsiveness was assessed by driving the EEG with click-tones at 20, 30 and 40Hz. We compared stimulus induced EEG changes between groups using spectral amplitude maps and a global measure of phase-locking (GFS). As expected, the 40Hz stimulation elicited the strongest changes. However, while controls and non-hallucinators increased 40Hz EEG activity during stimulation, a left-lateralized decrease was observed in the hallucinators. These differences were significant (p=.02). As expected, GFS increased during stimulation in controls (p=.08) and non-hallucinating patients (p=.06), which was significant when combining the two groups (p=.01). In contrast, GFS decreased with stimulation in hallucinating patients (p=0.13), resulting in a significantly different GFS response when comparing subjects with and without AVH (p<.01). Our data suggests that normally, 40Hz stimulation leads to the activation of a synchronized network representing the sensory input, but in hallucinating patients, the same stimulation partly disrupts ongoing activity in this network.     

Do antipsychotic medications decrease the risk of suicide in patients with schizophrenia?

The lifetime risk of suicide in persons with schizophrenia is much greater than that in the general population. The role of antipsychotic medications in decreasing suicide risk in schizophrenia has been little studied, and results often appear inconclusive and even confusing when issues such as dose-response effect are examined. Yet, evidence exists that both the traditional and newer antipsychotic medications reduce the risk of suicide and suicide attempts in schizophrenia. Because side effects are potentially significant risk factors in suicide, considerable incentive exists to examine whether newer antipsychotic agents that have a lower incidence of extrapyramidal side effects offer greater safety for this population.     

Meta-analysis and the science of schizophrenia: variant evidence or evidence of variants?

Quantification (meta-analysis) of the neuroscience evidence on schizophrenia shows very modest average differences between patient and control distributions across a great variety of measures and literatures. The strongest findings involve cognitive and psychophysiological measures. Several possible explanations for this situation are reviewed including technical immaturity, methodological variability, dimensional and multiple illness models and the nature of cognitive measurement. An argument is developed that biological subtypes and endophenotypes within the broad diagnostic category of schizophrenia underpin the meta-analytic evidence. Considerations in the use of this evidence to identify illness variants are described and four candidate subtypes are proposed. Schizophrenia is a disease that will resist biological definition until its variants are isolated and extracted from the generic patient population.     

Psychological therapy in schizophrenia: what is the evidence?

OBJECTIVE: The present contribution provides a critical outline of the current position of psychological therapies in schizophrenia. METHOD: Therefore, empirical research into the efficacy of psychological interventions in the treatment of schizophrenic disorders has been reviewed. RESULTS: Four cognitive-behavioural approaches have emerged as preeminently effective, or at least especially promising, as adjuncts to pharmacotherapy, i.e. the training of social skills, cognitive training programs for the remediation of neurocognitive deficits, psychoeducative, coping-orientated interventions with patients and their families, and cognitive-behavioural therapy of residual symptoms. These approaches are discussed with regard to their efficacy in reducing relapse rates, psychopathology as well as cognitive and social disability. CONCLUSION: Open questions and possibilities for the further development of these approaches are considered and prognostications are made concerning the future of psychotherapy research in schizophrenia, notably in the light of changing conditions in public health care systems.     

Frontal areas contribute to reduced global coordination of resting-state gamma activities in drug-naïve patients with schizophrenia

Schizophrenia has been postulated to involve impaired neuronal cooperation in large-scale neural networks, including cortico-cortical circuitry. Alterations in gamma band oscillations have attracted a great deal of interest as they appear to represent a pathophysiological process of cortical dysfunction in schizophrenia. Gamma band oscillations reflect local cortical activities, and the synchronization of these activities among spatially distributed cortical areas has been suggested to play a central role in the formation of networks. To assess global coordination across spatially distributed brain regions, Omega complexity (OC) in multichannel EEG was proposed. Using OC, we investigated global coordination of resting-state EEG activities in both gamma (30-50 Hz) and below-gamma (1.5-30 Hz) bands in drug-na?ve patients with schizophrenia and investigated the effects of neuroleptic treatment. We found that gamma band OC was significantly higher in drug-na?ve patients with schizophrenia compared to control subjects and that a right frontal electrode (F3) contributed significantly to the higher OC. After neuroleptic treatment, reductions in the contribution of frontal electrodes to global OC in both bands correlated with the improvement of schizophrenia symptomatology. The present study suggests that frontal brain processes in schizophrenia were less coordinated with activity in the remaining brain. In addition, beneficial effects of neuroleptic treatment were accompanied by improvement of brain coordination predominantly due to changes in frontal regions. Our study provides new evidence of improper intrinsic brain integration in schizophrenia by investigating the resting-state gamma band activity.     

Grey matter,an endophenotype for schizophrenia? A voxel-based morphometry study in siblings of patients with schizophrenia

BackgroundGrey matter, both volume and concentration, has been proposed as an endophenotype for schizophrenia given a number of reports of grey matter abnormalities in relatives of patients with schizophrenia. However, previous studies on grey matter abnormalities in relatives have produced inconsistent results. The aim of the present study was to examine grey matter differences between controls and siblings of patients with schizophrenia and to examine whether the age, genetic loading or subclinical psychotic symptoms of selected individuals could explain the previously reported inconsistencies.MethodsWe compared the grey matter volume and grey matter concentration of healthy siblings of patients with schizophrenia and healthy controls matched for age, sex and education using voxel-based morphometry (VBM). Furthermore, we selected subsamples based on age (< 30 yr), genetic loading and subclinical psychotic symptoms to examine whether this would lead to different results.ResultsWe included 89 siblings and 69 controls in our study. The results showed that siblings and controls did not differ significantly on grey matter volume or concentration. Furthermore, specifically selecting participants based on age, genetic loading or subclinical psychotic symptoms did not alter these findings.LimitationsThe main limitation was that subdividing the sample resulted in smaller samples for the subanalyses. Furthermore, we used MRI data from 2 different scanner sites.ConclusionThese results indicate that grey matter measured through VBM might not be a suitable endophenotype for schizophrenia.     

Correlations of functional capacity and neuropsychological performance in older patients with schizophrenia: Evidence for specificity of relationships?

BACKGROUND: Neuropsychological (NP) performance is a consistent correlate of everyday functioning in schizophrenia, but it is unclear whether relationships between individual NP ability areas and domains of everyday functioning are general or specific. Assessments of real-world everyday functioning may be influenced by environmental and social factors (e.g., social security, disability status, opportunities and restrictions in living situations). This study examined the specificity of the relationships between different NP abilities and performance-based measures of social and living skills. METHODS: 181 ambulatory older (age>50) patients with schizophrenia were examined with NP tests measuring episodic and working memory, executive functioning, verbal fluency, and processing speed. All subjects performed tasks examining social (Social Skills Performance Assessment: SSPA) and everyday living (UCSD Performance Based Skills Assessment: UPSA) skills. RESULTS: Using canonical analysis, the NP variables were used to predict the functional capacity measures. The analysis found that 37% of the variance in the functional capacity and NP measures was shared, X(2) (54)=106.29, p<.001. Two canonical roots described the cognitive variables and the roots were differentially associated with everyday living and social skills. The root loading on processing speed, episodic memory, and executive functions were associated with UPSA scores, while the root loading on working and episodic memory and verbal fluency were associated most strongly with social competence. IMPLICATIONS: Social and everyday living skills deficits in patients with schizophrenia may reflect generally independent domains of functional outcome, linked through cognitive performance. The data suggest that somewhat different cognitive processes are associated with these two domains of functional capacity, although there appears to be some overlap, which may be due to the nature of the NP tests employed.     

Disturbed circadian rest-activity cycles in schizophrenia patients: an effect of drugs?

The circadian rest-activity cycle of schizophrenia patients stabilized for more than a year on monotherapy with a "classical" neuroleptic (haloperidol, flupentixol) or with the atypical neuroleptic clozapine was documented by continuous activity monitoring for 3-7 weeks. In this pilot study, the three patients treated with clozapine had remarkably highly ordered restactivity cycles, whereas the four patients on classical neuroleptics had minor to major circadian rhythm abnormalities. This is the first documentation of circadian rest-activity cycle disturbances in schizophrenia related to class of drug.     

Different distribution patterns of lymphocytes and microglia in the hippocampus of patients with residual versus paranoid schizophrenia: Further evidence for disease course-related immune alterations?

Certain cytokines have been identified in the peripheral blood as trait markers of schizophrenia, while others are considered relapse-related state markers. Furthermore, data from peripheral blood, cerebrospinal fluid (CSF) and nuclear imaging studies suggest that (1) blood–brain barrier (BBB) dysfunction (e.g., immigration of lymphocytes into brain tissue and intrathecal antibody production) correlates with the development of negative symptoms, while (2) the brain’s mononuclear phagocyte system (microglial cells) is activated during acute psychosis.Based on these neuroinflammatory hypotheses, we have quantified the numerical density of immunostained CD3+ T-lymphocytes, CD20+ B-lymphocytes, and HLA-DR+ microglial cells in the posterior hippocampus of 17 schizophrenia patients and 11 matched controls. Disease course-related immune alterations were considered by a separate analysis of residual (prevailing negative symptoms, n = 7) and paranoid (prominent positive symptoms, n = 10) schizophrenia cases.Higher densities of CD3+ and CD20+ lymphocytes were observed in residual versus paranoid schizophrenia (CD 3: left: P = 0.047, right: P = 0.038; CD20: left: P = 0.020, right: P = 0.010) and controls (CD3: left: P = 0.057, right: P = 0.069; CD20: left: P = 0.008, right: P = 0.006). In contrast, HLA-DR+ microglia were increased in paranoid schizophrenia versus residual schizophrenia (left: P = 0.030, right: P = 0.012). A similar trend emerged when this group was compared to controls (left: P = 0.090, right: P = 0.090).BBB impairment and infiltration of T cells and B cells may contribute to the pathophysiology of residual schizophrenia, while microglial activation seems to play a role in paranoid schizophrenia. The identification of diverse immune endophenotypes may facilitate the development of distinct anti-inflammatory schizophrenia therapies to normalize BBB function, (auto)antibody production or microglial activity.     

How do early stages of information processing influence social skills in patients with schizophrenia?

Persons with schizophrenia show deficits across a broad range of cognitive domains, and their social skill deficits are thought, to some extent, to be caused by cognitive dysfunction. In this study, we attempted to replicate the correlation between the early stages of information processing and non-verbal skills. Subjects for the study included 22 men and six women who met DSM-IV criteria for the diagnosis of schizophrenia. All subjects were attending a rehabilitation program at the day-treatment centers of their hospitals. Social skills were assessed using a structured role-play test. The Degraded-Continuous Performance Test (CPT) and Span of Apprehension Test (SPAN) were used. Non-verbal skills were significantly correlated with CPT-False Alarm Rate (the rate of commission errors of all trials) in multiple regression analysis, but the receiving-processing skills did not have any relation to CPT or SPAN score. Non-verbal skills may be related to early information-processing deficiency, especially the response-inhibiting system. Receiving and processing skills may be related to later stages of information processing, or may reflect not only 'molecular' stages of information processing (less complex and less integration task in a continuum of complexity of cognitive processes) but also other factors such as social learning.     

Comorbidity and pathophysiology of obsessive–compulsive disorder in schizophrenia: Is there evidence for a schizo-obsessive subtype of schizophrenia?

Epidemiologic and neurobiologic evidence suggests that patients with comorbid obsessive-compulsive disorder (OCD) and schizophrenia may represent a special category among patients with schizophrenia. Efforts to examine the neurobiology of this group have focused on neuroimaging studies and neuropsychologic testing. Convergent evidence suggests that there may be a specific pattern of neurobiologic dysfunction in this subgroup of patients accounting for symptom co-expression. This review indicates that future studies should distinguish among (1) apparent obsessive-compulsive symptoms (OCS) that occur only in the context of psychosis and that may overlap with psychotic phenomenology, representing a forme fruste of psychosis; (2) OCS occurring only in the prodromal phase of schizophrenia; (3) neuroleptic-induced OCS or OCD; and (4) OCS or frank OCD occurring concurrently with schizophrenia. We examine the evidence for a putative schizo-obsessive disorder and outline suggestions for identifying OCS in the presence of psychosis.