Christina Andreou

Longitudinal studies of cognition in first episode psychosis: a systematic review of the literature.

Although cognitive deficits are recognized as a core feature in schizophrenia, their evolution over the course of the illness is still debated. Longitudinal studies of cognition in patients after a first episode of psychosis (FEP) provide extremely useful information, in that they include an adequate and realistic baseline measure of cognitive performance, while at the same time minimizing the effect of confounding variables associated with chronicity. The aim of this systematic review was to summarize findings of studies assessing the longitudinal course of neuropsychological deficits in patients with FEP for durations of at least one year. Overall, the neuropsychological deficits that are present following a first episode of psychosis appeared to remain stable over time for periods of up to ten years, the only possible exception being verbal memory deficits, where there is some evidence of further deterioration over the long term. However, further studies are needed to confirm this conclusion, especially in the (somewhat inconsistently defined) domain of executive function. Improvements in psychopathology appear to positively influence the course of cognitive deficits, although the effects of antipsychotic medication are not as clear.

Increased Resting-State Gamma-Band Connectivity in First-Episode Schizophrenia

BACKGROUND Schizophrenia has long been suggested to represent a disorder with prominent neural dysconnectivity. Gamma-band oscillations are highly relevant in this context, due both to their proposed involvement in neuronal synchronization and to their association with neurotransmitter systems relevant for schizophrenia. Several task-related studies have confirmed reduced power and synchronization of gamma-band oscillations in schizophrenia, but it has been suggested that these findings might not apply to the resting state. The present study aimed to investigate resting-state gamma-band connectivity in patients with schizophrenia. METHODS Sixty-four channel resting-state electroencephalography (eyes closed) was recorded in 22 patients with first-episode schizophrenia and 22 healthy controls matched for age and gender. Orthogonalized power envelope correlation was used as a measure of connectivity across 80 cortical regions at 40 Hz. Mean connectivity at each region was compared across groups using the nonparametric randomization approach. Additionally, the network-based statistic was applied to identify affected networks in patients. RESULTS Patients displayed increased mean functional gamma-band connectivity compared to controls in the left rolandic operculum. Network-based analyses indicated increased connectivity in patients within a strongly lateralized network consisting mainly of left inferior frontal/orbitofrontal, lateral and medial temporal, and inferior parietal areas. Within this network, gamma-band connectivity was higher in patients with low positive and disorganization symptom levels. CONCLUSIONS The present study provides a link between resting-state gamma-band connectivity and the core symptoms of schizophrenia. The observed findings are different than those reported by task-related studies, suggesting that resting-state studies might reveal new aspects in the pathophysiology of schizophrenia.

Beyond the Usual Suspects: Positive Attitudes Towards Positive Symptoms Is Associated With Medication Noncompliance in Psychosis

Antipsychotic medication represents the treatment of choice in psychosis according to clinical guidelines. Nevertheless, studies show that half to almost three-quarter of all patients discontinue medication with antipsychotics after some time, a fact which is traditionally ascribed to side-effects, mistrust against the clinician and poor illness insight. The present study investigated whether positive attitudes toward psychotic symptoms (ie, gain from illness) represent a further factor for medication noncompliance. An anonymous online survey was set up in order to prevent conservative response biases that likely emerge in a clinical setting. Following an iterative selection process, data from a total of 113 patients with a likely diagnosis of schizophrenia and a history of antipsychotic treatment were retained for the final analyses (80%). While side-effect profile and mistrust emerged as the most frequent reasons for drug discontinuation, 28% of the sample reported gain from illness (eg, missing voices, feeling of power) as a motive for noncompliance. At least every fourth patient reported the following reasons: stigma (31%), mistrust against the physician/therapist (31%), and rejection of medication in general (28%). Approximately every fifth patient had discontinued antipsychotic treatment because of forgetfulness. On average, patients provided 4 different explanations for noncompliance. Ambivalence toward symptoms and treatment should thoroughly be considered when planning treatment in psychosis. While antipsychotic medication represents the evidence-based cornerstone of the current treatment in schizophrenia, further research is needed on nonpharmacological interventions for noncompliant patients who are willing to undergo intervention but refuse pharmacotherapy.

Dopaminergic Modulation of Probabilistic Reasoning and Overconfidence in Errors: A Double-Blind Study

INTRODUCTION Reasoning biases such as jumping to conclusions (JTC) and overconfidence in errors have been well replicated in patients with delusions. However, their relation to dopaminergic activity, central to pathophysiologic models of psychosis, has not yet been investigated. This study aimed to examine the effects of a dopaminergic agonist (L-dopa) and a dopaminergic antagonist (haloperidol) on the JTC bias and overconfidence in errors after single-dose administration in healthy individuals. METHODS The study used a randomized, double-blind, placebo-controlled, 3-way crossover design. Participants were 36 healthy individuals aged 18-36 years. The variables of interest were draws to decision and probability threshold to decision on a computerized variant of the beads task and the number of high-confident incorrect responses on a visual memory task. RESULTS There were no significant effects of substance on draws to decision and probability threshold to decision. A significant effect emerged for high-confident incorrect responses in the memory task; pairwise comparisons indicated a significant reduction of the number of high-confident incorrect responses after administration of haloperidol vs l-dopa and placebo. CONCLUSIONS This is the first study to investigate the direct effects of dopaminergic drugs on reasoning biases. The JTC bias and overconfidence in errors showed a differential pattern of dopaminergic modulation, suggesting that they represent different facets of reasoning abnormalities that interact with each other to produce delusions in susceptible individuals.

Deficits in sustained attention in schizophrenia but not in bipolar disorder

The aim of the present study was to investigate sustained attention in remitted patients with bipolar disorder and in patients with schizophrenia, as compared to each other and to healthy controls; a secondary aim was to investigate the correlations of different symptom dimensions with performance on sustained attention in the two patient groups. Participants were 29 (18 men) outpatients with schizophrenia (SZ), 19 (8 men) patients with bipolar disorder I (BP) in remission, and 30 (15 men) healthy controls (HC); all three groups were matched on age, sex ratio, and level of education. Symptom severity (positive symptoms, negative symptoms, and general psychopathology) of patients with SZ were assessed with the Greek version of the Positive and Negative Syndrome Scale (PANSS); residual affective symptoms of patients with BP were assessed with the Young Mania Rating Scale (YMRS) and the Montgomery-Asberg Depression Rating Scale (MADRS). Sustained attention was measured by means of the Penn Continuous Performance Test (PCPT). The three groups differed significantly on the PCPT scores. Patients with SZ performed more poorly than both the BP and HC groups, whereas patients with BP did not differ significantly from HC. Performance on the PCPT did not correlate significantly with scores on the YMRS and MADRS in patients with BP. Also, scores on the PCPT did not correlate significantly with scores on any of the three subscales of the PANSS. Outpatients with schizophrenia presented deficits in sustained attention, whereas patients with bipolar disorder I in remission did not manifest such impairment. These results imply that impaired sustained attention might be a more enduring deficit in schizophrenia than it appears to be in bipolar disorder.

Resting-state connectivity in the prodromal phase of schizophrenia: Insights from EEG microstates

INTRODUCTION Resting-state EEG microstates are thought to reflect the momentary local states and interactions of distributed neural networks in the brain. Several changes in resting-state EEG microstates have been described in acutely ill patients with schizophrenia, but it is not known whether these represent trait or state abnormalities. The present study aimed to investigate this issue by assessing EEG microstate characteristics in high-risk individuals (HR) and clinically stable first-episode patients with schizophrenia (SZ) with low symptom levels, compared to each other and healthy controls (HC). METHOD Participants were 18 HR, 18 SZ, and 22 HC subjects. 64-channel resting-state EEG recordings were used for microstate analyses. Microstates were clustered into four classes (A-D) according to their topography. Temporal parameters and topographies of microstates were compared among groups. RESULTS Microstate class A displayed higher coverage and occurrence in HR than SZ and HC, while microstate class B covered significantly more time in SZ compared to both HR and HC. Microstate class B displayed an aberrant spatial configuration in SZ, and to a lesser extent also in HR, compared to HC, with patients exhibiting significantly higher activity in the vicinity of the left posterior cingulate. DISCUSSION Microstate abnormalities observed in HR were similar to those previously reported in acutely ill patients with schizophrenia. Moreover, there was evidence that HR and SZ might share specific disturbances in brain functional connectivity. These findings raise the possibility that certain abnormalities in resting-state EEG microstates might be associated with an increased risk for psychosis.

The predictive significance of neurocognitive factors for functional outcome in bipolar disorder.

Purpose of review Poor psychosocial functioning in bipolar disorder often persists even after affective symptom remission. Cognitive deficits, which have emerged as a core feature of bipolar disorder in the past few years, are among the factors implicated in adverse psychosocial outcomes of patients suffering from bipolar disorder. This review aims to overview recent literature on the association of neurocognition and psychosocial functioning in bipolar disorder. Recent findings Cognitive deficits (mainly general neurocognitive functioning, attention and verbal learning and memory) are important determinants of poor psychosocial functioning in bipolar disorder, although to a lesser extent than in schizophrenia. Although affective symptoms appear to be a more important predictor of functional outcome in symptomatic patients, cognitive deficits also play a significant role, more readily recognizable in euthymic or chronic patients. Summary Given the importance of cognitive impairments for psychosocial outcomes in bipolar disorder, the development of interventions targeting cognitive impairments is imperative for improving recovery rates and quality of life in patients, even after adequate symptom control.

Can We Trust the Internet to Measure Psychotic Symptoms

Online studies are increasingly utilized in applied research. However, lack of external diagnostic verification in many of these investigations is seen as a threat to the reliability of the data. The present study examined the robustness of internet studies on psychosis against simulation. We compared the psychometric properties of the Community Assessment of Psychic Experiences scale (CAPE), a self-report instrument measuring psychotic symptoms, across three independent samples: (1) participants with a confirmed diagnosis of schizophrenia, (2) participants with self-reported schizophrenia who were recruited over the internet, and (3) clinical experts on schizophrenia as well as students who were asked to simulate a person with schizophrenia when completing the CAPE. The CAPE was complemented by a newly developed 4-item psychosis lie scale. Results demonstrate that experts asked to simulate schizophrenia symptoms could be distinguished from real patients: simulators overreported positive symptoms and showed elevated scores on the psychosis lie scale. The present study suggests that simulated answers in online studies on psychosis can be distinguished from authentic responses. Researchers conducting clinical online studies are advised to adopt a number of methodological precautions and to compare the psychometric properties of online studies to established clinical indices to assert the validity of their results.

Response confidence for emotion perception in schizophrenia using a Continuous Facial Sequence Task

Deficits in emotion perception and overconfidence in errors are well-documented in schizophrenia but have not been examined concurrently. The present study aimed to fill this gap. Twenty-three schizophrenia patients and twenty-nine healthy subjects underwent a Continuous Facial Sequence Task (CFST). The CFST comprised two blocks: a female (1st block) and a male protagonist (2nd block) displayed the six basic emotions postulated by Ekman as well as two more complex mental states and a neutral expression. Participants were first asked to identify the affect displayed by the performer and then to judge their response confidence. No group differences emerged regarding overall emotion perception. Follow-up analyses showed that patients were less correct in detecting some negative emotions but performed better for neutral or positive emotions. Regarding confidence, incorrect decisions in patients were associated with higher confidence than in controls (statistical trend level, moderate effect size). Patients displayed significant overconfidence in errors for negative emotions. In addition, patients were more prone to high-confident errors for emotions that were displayed in weak emotional intensity. While the study supports the view that the examination of confidence adds unique information to our understanding of social cognition, several methodological limitations render its findings preliminary.

Relationship between Oscillatory Neuronal Activity during Reward Processing and Trait Impulsivity and Sensation Seeking

Background The processing of reward and punishment stimuli in humans appears to involve brain oscillatory activity of several frequencies, probably each with a distinct function. The exact nature of associations of these electrophysiological measures with impulsive or risk-seeking personality traits is not completely clear. Thus, the aim of the present study was to investigate event-related oscillatory activity during reward processing across a wide spectrum of frequencies, and its associations with impulsivity and sensation seeking in healthy subjects. Methods During recording of a 32-channel EEG 22 healthy volunteers were characterized with the Barratt Impulsiveness and the Sensation Seeking Scale and performed a computerized two-choice gambling task comprising different feedback options with positive vs. negative valence (gain or loss) and high or low magnitude (5 vs. 25 points). Results We observed greater increases of amplitudes of the feedback-related negativity and of activity in the theta, alpha and low-beta frequency range following loss feedback and, in contrast, greater increase of activity in the high-beta frequency range following gain feedback. Significant magnitude effects were observed for theta and delta oscillations, indicating greater amplitudes upon feedback concerning large stakes. The theta amplitude changes during loss were negatively correlated with motor impulsivity scores, whereas alpha and low-beta increase upon loss and high-beta increase upon gain were positively correlated with various dimensions of sensation seeking. Conclusions The findings suggest that the processing of feedback information involves several distinct processes, which are subserved by oscillations of different frequencies and are associated with different personality traits.