Elevated noise power in gamma band related to negative symptoms and memory deficit in schizophrenia

Background

There is an increasing consideration for a disorganized cerebral activity in schizophrenia, perhaps relating to a synaptic inhibitory deficit in the illness. Noise power (scalp-recorded electroencephalographic activity unlocked to stimuli) may offer a non-invasive window to assess this possibility.

Methods

29 minimally-treated patients with schizophrenia (of which 17 were first episodes) and 27 healthy controls underwent clinical and cognitive assessments and an electroencephalographic recording during a P300 paradigm to calculate signal-to-noise ratio and noise power magnitudes in the theta and gamma bands.

Results

In comparison to controls, a significantly higher gamma noise power was common to minimally-treated and first episode patients over P3, P4, T5 and Fz electrode sites. Those high values were directly correlated to negative symptom severity and inversely correlated to verbal memory scores in the patients. There were no differences in signal-to-noise ratio magnitudes among the groups. Gamma noise power at Fz discriminated significantly between patients and controls. No significant differences were found in theta noise power or in gamma noise power over the other electrode sites between the groups of patients and controls.

Limitations

We have not assessed phase-locked and non-phase locked power changes, a complementary approach that may yield useful information.

Conclusions

Gamma noise power may represent a useful and non-invasive tool for studying brain dysfunction in psychotic illness. These results suggest an inefficient activation pattern in schizophrenia.     

Gender-specific associations of depression with positive and negative symptoms in acute schizophrenia

This clinical study analyzed gender-specific relationships of depression with other psychopathological and clinical variables in hospitalized patients with schizophrenia. During clinical routine treatment 119 inpatients with acute schizophrenia (DSM-IV) were investigated with the Calgary Depression Rating Scale for Schizophrenia (CDSS), the Clinical Global Impressions (CGI), and the Positive and Negative Syndrome Scale (PANSS). Depression scores of 77 male and 42 female patients (mean age 31.6+/-10.3 years) were related to background variables and to positive and negative symptom scores. Mean CDSS (5.8+/-5.6) and PANSS scores (total 76.9+/-22.1, positive symptoms 17.6+/-7.6, negative symptoms 20.5+/-7.8) were not significantly different between males and females. In females, depression was independently associated with higher negative symptom scores (P<0.01) and younger age (P<0.05) whereas in males positive symptoms (P<0.05) and short hospitalization (P<0.05) were the main factors associated with depression. The study revealed gender-specific differences in the relationship of depression with negative and positive symptoms.     

Investigation of serum BDNF levels in drug-naive patients with schizophrenia

The role of brain-derived neurotrophic factor (BDNF) is to promote and modulate the neuronal responses across neurotransmitter systems in the brain. Therefore, abnormal BDNF signaling may be associated with the pathophysiology of schizophrenia. Decreased BDNF levels in the brain and the serum of patients with psychotic disorders have been reported. In the present study, we assessed serum BDNF levels in a group of 14 drug-naive first-episode patients with schizophrenia (FEP), compared to 15 healthy controls. The serum BDNF levels in the sample of FEP patients was significantly reduced compared to normal controls (23.92+/-5.99 ng/ml vs. 30.0+/-8.43 ng/ml, F=5.01, df=1, p=.034). Negative correlations were shown between serum BDNF levels of the patients and the PANSS Positive and Negative subscale scores. Our findings indicate that BDNF levels at the onset of schizophrenia may reflect associated pathophysiological processes as well as the severity of positive and negative psychotic symptoms.     

Elevated plasma superoxide dismutase in first-episode and drug naive patients with schizophrenia: inverse association with positive symptoms

Excessive free radical production or oxidative stress may be involved in the pathophysiology of schizophrenia as evidenced by increased superoxide dismutase (SOD) activities, a critical enzyme in the detoxification of superoxide radicals. This study compared plasma SOD activities in 78 never-medicated first-episode and 100 medicated chronic schizophrenia patients to 100 healthy control subjects and correlated these SOD activities with the Positive and Negative Syndrome Scale (PANSS) among the schizophrenic patients. We found that both first-episode and chronic patients had significantly increased plasma SOD activities compared to controls, and that chronic schizophrenic patients on antipsychotic medication had significantly higher SOD activities than first episode schizophrenic patients. Plasma SOD activities were also negatively correlated with positive symptoms of schizophrenia, but only in first-episode patients. Thus, oxidative stress appears to be greater in first episode schizophrenic patients with fewer positive symptoms and may become greater as schizophrenia becomes more chronic, although we cannot exclude the possibility that chronic antipsychotic treatment may increase SOD activities and presumed oxidative stress in schizophrenia.     

Subcortical brain volumes relate to neurocognition in schizophrenia and bipolar disorder and healthy controls

Background

Similar patterns of subcortical brain abnormalities and neurocognitive dysfunction have been demonstrated in schizophrenia and bipolar disorder, with more extensive findings in schizophrenia. It is unknown whether relationships between subcortical volumes and neurocognitive performance are similar or different between schizophrenia and bipolar disorder.

Methods

MRI scans and neuropsychological test performance were obtained from 117 schizophrenia or 121 bipolar spectrum disorder patients and 192 healthy control subjects. Using the FreeSurfer software, volumes of 18 selected subcortical structures were automatically segmented and analyzed for relationships with results from 7 neurocognitive tests.

Results

In schizophrenia, larger left ventricular volumes were related to poorer motor speed, and bilateral putamen volumes were related to poorer verbal learning, executive functioning and working memory performance. In bipolar disorder, larger left ventricular volumes were related to poorer motor speed and executive functioning. The relationship between left putamen volume and working memory was specific to schizophrenia. The relationships between left inferior lateral ventricles and motor speed and between right putamen volumes and executive functioning were similar in schizophrenia and bipolar disorder, and different from healthy controls. The results remained significant after corrections for use of antipsychotic medication. Significant structure-function relationships were also found when all subjects were combined into one group.

Conclusion

The present findings suggest that there are differences as well as similarities in subcortical structure/function relationships between patients with schizophrenia or bipolar disorder and healthy individuals. The observed differences further suggest that ventricular and putamen volume sizes may reflect severity of cognitive dysfunction in these disorders.     

Neurocognitive,clinical and functional correlates of subjective quality of life in Asian outpatients with schizophrenia

Quality of life (QOL) impairment is evident in patients with schizophrenia and is increasingly recognised as an important evaluation criterion of treatment outcome. Hence, this study aimed to identify the neurocognitive, clinical and functional parameters associated with subjective QOL in patients with schizophrenia within an Asian context, and specifically in an outpatient setting. This study was conducted on 83 outpatients with DSM-IV diagnosis of schizophrenia, and 47 age- and gender-matched healthy controls. All participants were administered with the World Health Organisation Quality of Life Assessment-Brief Form (WHOQOL-BREF) and Brief Assessment of Cognition in Schizophrenia (BACS), to measure quality of life and cognitive function respectively. Patients were also assessed for severity of psychopathology, as well as level of psychosocial functioning, using the Positive and Negative Syndrome Scale (PANSS) and Global Assessment of Functioning (GAF) rating scales respectively. Specific psychopathology (greater severity of PANSS negative symptoms, general psychopathology subscale scores), cognitive deficits (working and verbal memories), and lower GAF scores were correlated with poorer QOL in patients. Multivariate analyses revealed that younger age, being single and lower level of psychosocial functioning were associated with poorer QOL but level of psychosocial functioning did not appear to mediate the effects of symptoms and neurocognitive deficits on QOL. Overall, this study highlighted the need for clinicians to pay more attention to these clinical, neurocognitive and functional parameters and their integrative relationships with QOL in order to optimise the treatment outcomes of patients with schizophrenia.     

Obsessive compulsive disorder and symptoms may have different effects on schizophrenia

The aim of this study is to investigate the possible different effects of obsessive compulsive disorder (OCD) and obsessive compulsive symptoms (OCS) on schizophrenia illness in regard to clinical characteristics such as severity of symptomatology.We included 184 patients with schizophrenia on monotherapy with a stable dose of antipsychotics for at least three months. Severity of clinical symptoms was evaluated by Positive and Negative Syndrome Scale. OCS was examined by Yale-Brown Obsessive Compulsive Scale (Y-BOCS) Checklist. We also assessed OCD by using Y-BOCS.Seventeen percent of the patients were diagnosed with current OCD, while 17.4% of the patients were found to have OCS without OCD. Age of onset for OCD group was earlier than non-OCS group (p = 0.007).The rate of occupation was higher (p = 0.001), prevalence of other comorbid psychiatric disorders was lower (p = 0.05), number of hospitalization was lower (p = 0.03), GAF score was higher (p = 0.03) and duration of education was longer (p = 0.02) in the OCS group than in the non-OCS group. The rate of occupation was higher (p = 0.04) and that rate of comorbid psychiatric disorders was lower (p = 0.01) in the OCS group than in the OCD group. We found more OCS in patients using atypical antipsychotics (p = 0.03).Our findings suggest that OCD and OCS might have different effects on schizophrenia.     

Cognitive training for divergent thinking in schizophrenia: A pilot study

Individuals with schizophrenia demonstrate deficits in divergent thinking. This ability is indispensable for generating creative solutions and navigating the complexities of social interactions. In a pilot study, seventeen stable schizophrenia outpatients were randomly assigned to a training program for divergent thinking or a control program on convergent thinking. After eight weeks of training, participants in the divergent thinking program had significantly greater improvements on measures of idea fluency, negative symptoms, and interpersonal relations than did participants receiving the control program. These preliminary results suggest that interventions for divergent thinking in schizophrenia may lead to improvements in patients' social functioning.     

Auditory and visual P300 reflecting cognitive improvement in patients with schizophrenia with quetiapine: A pilot study

We recorded event-related potentials (ERPs) in patients with schizophrenia before and after treatment with quetiapine, to investigate this drug's effects on cognitive function. Auditory and visual oddball stimulus discrimination paradigms were presented to patients with schizophrenia (N = 20) before and after 3 months' treatment with quetiapine. The 2-stimulus auditory oddball paradigm used a standard tone (1000 Hz, 75 dB, 80%) and a target tone (2000 Hz, 75 dB, 20%). The 2-stimulus visual oddball paradigm used a standard stimulus (small circle, 80%) and a target stimulus (large circle, 20%). Patients' severity of psychopathology was initially evaluated with the Positive and Negative Syndrome Scale (PANSS) and was likewise re-evaluated after treatment. After treatment with quetiapine, patients' P300 amplitudes increased over baseline for both tasks (auditory stimuli, P < 0.01; visual stimuli, P < 0.01) and their P300 latencies for both target stimuli decreased significantly (auditory stimuli, P < 0.001; visual stimuli, P < 0.01). Visual P300 amplitude was negatively correlated with the severity of positive symptoms at the Fz electrode before the treatment (r = − 0.45, P < 0.05). After treatment with quetiapine, there were no significant correlations between severity of positive or negative symptoms and visual P300 amplitudes for midline electrodes. These findings suggest that the reduced and delayed P300 may be a state marker for schizophrenia, which may in turn be modulated by positive symptoms, and also suggest that the amplitude and latency for both auditory and visual tasks may be decreased by quetiapine treatment. Based on these results, we suggest that the atypical antipsychotic quetiapine may improve some aspects of cognitive domains in patients with schizophrenia.     

Verbal learning contributes to cognitive insight in schizophrenia independently of affective and psychotic symptoms

Objective

Patients with schizophrenia exhibit distorted beliefs and experiences, and their own evaluation of this is labeled cognitive insight. We examined the relationship between cognitive insight and neurocognition, as well as the contribution of neurocognition in explaining cognitive insight.

Method

Clinically characterized patients with schizophrenia (n = 102) were assessed with a measure of cognitive insight, Beck Cognitive Insight Scale (BCIS) and a neuropsychological test battery. The contribution of neurocognition to the explained variance in BCIS components self-reflectiveness (i.e. objectivity and reflectiveness) and self-certainty (i.e. overconfidence in own beliefs) was examined controlling for current affective and psychotic symptoms.

Results

A significant negative correlation was found between self-certainty and verbal learning, whereas no associations were found between self-reflectiveness and any of the neuropsychological tests. Verbal learning was added significantly to the explained variance in self-certainty after controlling for potential confounders.

Conclusion

High self-certainty was associated with poor verbal learning. This suggests that overconfidence in own beliefs is associated with cognitive dysfunction in schizophrenia.     

Auditory orienting and inhibition of return in schizophrenia: A functional magnetic resonance imaging study

Patients with schizophrenia (SP) exhibit deficits in both attentional reorienting and inhibition of return (IOR) during visual tasks. However, it is currently unknown whether these deficits are supramodal in nature and how these deficits relate to other domains of cognitive dysfunction. In addition, the neuronal correlates of this pathological orienting response have not been investigated in either the visual or auditory modality. Therefore, 30 SP and 30 healthy controls (HC) were evaluated with an extensive clinical protocol and functional magnetic resonance imaging (fMRI) during an auditory cuing paradigm. SP exhibited both increased costs and delayed IOR during auditory orienting, suggesting a prolonged interval for attentional disengagement from cued locations. Moreover, a delay in the development of IOR was associated with cognitive deficits on formal neuropsychological testing in the domains of attention/inhibition and working memory. Event-related fMRI showed the characteristic activation of a frontoparietal network (invalid trials > valid trials), but there were no differences in functional activation between patients and HC during either attentional reorienting or IOR. Current results suggest that orienting deficits are supramodal in nature in SP, and are related to higher-order cognitive deficits that directly interfere with day-to-day functioning.     

Effects of haloperidol on cognition in schizophrenia patients depend on baseline performance: a saccadic eye movement study

Schizophrenic patients are heterogeneous with respect to voluntary eye movement performance, with some showing impairment (e.g., high antisaccade error rates) and others having intact performance. To investigate how this heterogeneity may correlate with different cognitive outcomes after treatment, we used a prosaccade and antisaccade task to investigate the effects of haloperidol in schizophrenic subjects at three time points: baseline (before medication), 3-5 days post-medication, and 12-14 days post-medication. We also investigated changes on the Stroop Task and the Positive and Negative Syndrome Scale (PANSS) in these same subjects. Results were compared to matched controls. When considered as a single patient group, haloperidol had no effects across sessions on reflexive and voluntary saccadic eye movements of schizophrenic patients. In contrast, the performance of the Control group improved slightly but significantly across sessions on the voluntary eye movement task. When each subject was considered separately, interestingly, for schizophrenic patients change in voluntary eye movement performance across sessions depended on the baseline performance in a non-monotonic manner. That is, there was maximal worsening of voluntary eye movement performance at an intermediate level of baseline performance and the worsening decreased on either side of this intermediate baseline level. When patients were divided into categorical subgroups (nonimpaired and impaired), consistent with the non-monotonic relationship, haloperidol worsened voluntary eye movement performance in the nonimpaired patients and improved performance in the impaired patients. These results were only partially reflected in the Stroop Test. Both patient subgroups showed clinically significant improvement over time as measured by the PANSS. These findings suggest that haloperidol has different effects on cognitive performance in impaired and nonimpaired schizophrenic patients that are not evident in clinical ratings based on the PANSS. Given that good cognitive function is important for long-term prognosis and that there is heterogeneity in schizophrenia, these findings are critical for optimal evaluation and treatment of schizophrenic patients.     

Abnormal prediction error is associated with negative and depressive symptoms in schizophrenia

Prediction error in learning is where learning occurs to the degree to which an outcome consequent to a stimulus is surprising. It has been suggested that abnormal use of prediction error in schizophrenia may underlie the formation of inappropriate associations giving rise to psychotic symptoms. Kamin blocking is a phenomenon that demonstrates prediction error. Kamin blocking is shown where prior learning about a stimulus A paired with an outcome retards learning about a stimulus B when presented subsequently as part of a stimulus compound AB paired with the same outcome. Prior studies have indicated reduced Kamin blocking in schizophrenia specifically in non-paranoid patients. It is however unclear how reduced Kamin blocking is associated with specific symptoms in schizophrenia. The present study examined Kamin blocking performance in a high functioning community-based sample of 34 people with schizophrenia and 48 controls closely matched for pre-morbid IQ. In these patients we measured Kamin blocking and symptoms using positive and negative symptom scales (PANSS) and Scale for the Assessment of Negative Symptoms (SANS) and Scale for the Assessment of Positive Symptoms (SAPS). Results confirmed that people with schizophrenia had significantly reduced Kamin blocking. Kamin blocking performance was associated with negative and depressive symptoms. These associations with symptoms were crucially not found with baseline associative learning or unblocking measures, confirming specificity to the Kamin blocking effect. These data demonstrate first that abnormal prediction error as assessed in the Kamin blocking task is associated with negative and depressive symptoms rather than positive symptoms in high functioning schizophrenia patients. Second this strongly suggests that reduced Kamin blocking may be useful as an animal model of specific relevance to negative and depressive symptoms in schizophrenia.     

Mirtazapine augmentation enhances cognitive and reduces negative symptoms in schizophrenia patients treated with risperidone: a randomized controlled trial

This preliminary study aimed to determine if adding mirtazapine to risperidone might improve negative and cognitive symptoms in schizophrenia. In an 8-week, double-blind clinical trial, we randomly assigned 21 stabilized outpatients with schizophrenia undergoing risperidone treatment to adjunctive treatment with either mirtazapine or a placebo. The mirtazapine group exhibited a statistically significant improvement in cognitive function, including vocabulary and immediate memory, and negative symptoms (as measured by negative symptom scales) and showed an adverse effect of 5.83 kg mean weight gain. This study suggests augmenting risperidone with mirtazapine can effectively improve both negative and some cognitive symptoms of schizophrenia.

Research highlights

? Mirtazapine enhances some cognitive symptoms of schizophrenia. ? Mirtazapine reduces negative symptoms of schizophrenia.     

Effectiveness of risperidone long-acting injection in first-episode schizophrenia: in naturalistic setting

Patients with first-episode schizophrenia frequently relapse during the first years of the illness. This may be associated with clinical deterioration. It is important to prevent relapses in first-episode schizophrenia. We examine whether risperidone long-acting injection (RLAI) could effectively act to prevent relapse in first-episode schizophrenia. We conducted a prospective, naturalistic, controlled, and open-label study over 2 years in 50 patients with first-episode schizophrenia. 22 patients with schizophrenia were assigned to the RLAI group and 28 patients with schizophrenia to the oral risperidone group as control. We compared medication adherence, time to non-adherence, and relapse rate between the RLAI and control groups. There were no significant difference in sociodemographic findings and initial psychometric measures between two groups. The RLAI group showed significantly lower relapse rate and higher medication adherence than the control group. The result demonstrated by Kaplan-Meier survival analysis that time to non-adherence is associated with the difference in the groups. Cox proportional survival analysis revealed that time from baseline to relapse was associated with time to non-adherence. This result showed that RLAI could be effective in maintaining medication adherence and preventing relapse. However, studies with a larger sample size will be needed to examine whether these results are applicable to schizophrenic population.     

Anterior insular volume is larger in patients with obsessive-compulsive disorder

There has been increasing evidence indicating gray matter abnormalities in patients with obsessive-compulsive disorder (OCD). Several voxel-based morphometry (VBM) studies have reported volume changes in the insular cortex. Although there are distinct differences in the connectivity and functions in the anterior and posterior insular cortices, these two regions have never been distinguished in previous VBM studies. In this study, we adopted a region of interest (ROI) method to measure insular volume separately. We investigated insular volume in 32 drug-free patients with OCD and in 34 healthy controls using magnetic resonance imaging (MRI). Repeated measures multivariate analysis of covariance (MANCOVA) was conducted to examine the difference between the patients and the controls. Compared with the healthy controls, the patients had a significantly larger gray matter volume in the anterior insular cortex bilaterally (post hoc test, p = 0.036; left, p = 0.047; right). This is the first volumetric MRI study to separately investigate the anterior and posterior insular cortex volumes in non-medicated patients with OCD. The results suggest that the anterior insular cortex may be related to the pathophysiology of OCD.     

Reduced cardio-respiratory coupling indicates suppression of vagal activity in healthy relatives of patients with schizophrenia

Previous studies have observed reduced vagal modulation in patients with acute schizophrenia and their first-degree relatives, thus suggesting a genetic predisposition.     

Relative contribution of antipsychotics,negative symptoms and executive functions to social functioning in stable schizophrenia

The purpose of this study was to examine the relative contributions of antipsychotic medication, negative symptoms and executive functions to impairment in social functioning in a sample of outpatients with stable schizophrenia.     

Longitudinal alterations of executive function in non-psychotic adolescents at familial risk for schizophrenia

Genetic diathesis to schizophrenia may involve alterations of adolescent neurodevelopment manifesting as cognitive deficits. Brain regions mediating executive function (fronto-striatal circuits) develop during adolescence while those supporting elementary aspects of attention (e.g. sustained focused attention) have a more protracted maturation beginning in childhood. We hence predicted that adolescents at risk for schizophrenia would show a failure of normal maturation of executive function. We prospectively assessed 18 offspring and 6 siblings of schizophrenia patients (HR) and 28 healthy controls at baseline, year-1 and year-2 follow-up using the Continuous Performance Test [visual-d′] and Wisconsin Card Sort Test (WCST). Perseverative errors on the WCST in HR remained stable but decreased in controls over the follow-up (study-group by assessment–time interaction, p = 0.01, controlling for IQ). No significant study-group by assessment-time interactions were seen for sustained attentional performance. HR may not improve while healthy subjects progressively improve on executive function during adolescence and early adulthood. Our results suggest an altered maturational trajectory of executive function during adolescence in individuals at familial risk for schizophrenia.     

Insular cortex volume and impulsivity in teenagers with first-presentation borderline personality disorder

Fronto-limbic neural dysfunction has been implicated in the emotional dysregulation and impulsivity seen in borderline personality disorder (BPD). However, it remains unclear whether affected individuals exhibit morphologic changes of the insular cortex, a fronto-limbic integration cortex engaged in emotional regulation and impulse control. This magnetic resonance imaging study examined the insular cortex volume and its relationship to clinical characteristics in a first-presentation teenage BPD sample. No significant difference was found in the insular volume between 20 BPD participants (5 males) and 20 healthy control participants (5 males). There was no association between the insular volume and parasuicidal episodes, trauma exposure, or comorbid Axis I disorders, but the BPD participants with violent episodes during the previous 6 months had a smaller insular volume bilaterally compared with those without such episodes. Furthermore, right anterior insular volume in the BPD participants was negatively correlated with impulsivity score. These preliminary findings suggest that insular cortex volume does not significantly differ in early BPD, but that there might be a relationship with violent and impulsive behavior that is often seen in the disorder. Further studies are needed to clarify whether the potential relationship between the insular cortex volume and impulsivity is specific to BPD.