Investigation of metamemory functioning in the at-risk mental state for psychosis.

BACKGROUND: Metamemory describes the monitoring and knowledge about one's memory capabilities. Patients with schizophrenia have been found to be less able in differentiating between correct and false answers (smaller confidence gap) when asked to provide retrospective confidence ratings in previous studies. Furthermore, higher proportions of very-high-confident but false responses have been found in this patient group (high knowledge corruption). Whether and how these biases contribute to the early pathogenesis of psychosis is yet unclear. This study thus aimed at investigating metamemory function in the early course of psychosis. METHOD: Patients in an at-risk mental state for psychosis (ARMS, n = 34), patients with a first episode of psychosis (FEP, n = 21) and healthy controls (HCs, n = 38) were compared on a verbal recognition task combined with retrospective confidence-level ratings. RESULTS: FEP patients showed the smallest confidence gap, followed by ARMS patients, followed by HCs. All groups differed significantly from each other. Regarding knowledge corruption, FEP patients differed significantly from HCs, whereas a statistical trend was revealed in comparison of ARMS and FEP groups. Correlations were revealed between metamemory, measures of positive symptoms and working memory performance. CONCLUSIONS: These data underline the presence of a metamemory bias in ARMS patients which is even more pronounced in FEP patients. The bias might represent an early cognitive marker of the beginning psychotic state. Longitudinal studies are needed to unravel whether metacognitive deficits predict the transition to psychosis and to evaluate therapeutic interventions.

Effects of a genome-wide supported psychosis risk variant on neural activation during a theory-of-mind task.

Schizophrenia is associated with marked deficits in theory of mind (ToM), a higher-order form of social cognition representing the thoughts, emotions and intentions of others. Altered brain activation in the medial prefrontal cortex and temporo-parietal cortex during ToM tasks has been found in patients with schizophrenia, but the relevance of these neuroimaging findings for the heritable risk for schizophrenia is unclear. We tested the hypothesis that activation of the ToM network is altered in healthy risk allele carriers of the single-nucleotide polymorphism rs1344706 in the gene ZNF804A, a recently discovered risk variant for psychosis with genome-wide support. In all, 109 healthy volunteers of both sexes in Hardy-Weinberg equilibrium for rs1344706 were investigated with functional magnetic resonance imaging during a ToM task. As hypothesised, risk carriers exhibited a significant (P<0.05 false discovery rate, corrected for multiple comparisons) risk allele dose effect on neural activity in the medial prefrontal cortex and left temporo-parietal cortex. Moreover, the same effect was found in the left inferior parietal cortex and left inferior frontal cortex, which are part of the human analogue of the mirror neuron system. In addition, in an exploratory analysis (P<0.001 uncorrected), we found evidence for aberrant functional connectivity between the frontal and temporo-parietal regions in risk allele carriers. To conclude, we show that a dysfunction of the ToM network is associated with a genome-wide supported genetic risk variant for schizophrenia and has promise as an intermediate phenotype that can be mined for the development of biological interventions targeted to social dysfunction in psychiatry.

Neural substrates of pleiotropic action of genetic variation in COMT: a meta-analysis.

Genetic variation in catechol-O-methyltransferase (COMT), encoding an enzyme critical for prefrontal dopamine flux, has been studied extensively using both behavioral and neuroimaging methods. In behavior, pleiotropic action of a functional Val(158)Met (rs4680) polymorphism on executive cognition and emotional stability has been described and proposed to be of evolutionary significance (the 'warrior/worrier' hypothesis). We conducted a meta-analysis of all available neuroimaging studies of rs4680 to investigate the evidence for a neural substrate of this behavioral pleiotropy. We show significant association between the COMT genotype and prefrontal activation, with large (d=0.73) effect size without evidence for publication bias. Strong and opposing effects were found for executive cognition paradigms (favoring Met allele carriers) and emotional paradigms (favoring Val), providing meta-analytical evidence for a neural substrate for the pleiotropic behavioral effects of COMT genetic variation and validating the use of intermediate phenotypes as a method to bridge between genes and behavior.

Neuronal correlates of affective theory of mind in schizophrenia out-patients: evidence for a baseline deficit.

BACKGROUND: Schizophrenia out-patients have deficits in affective theory of mind (ToM) but also on more basal levels of social cognition, such as the processing of neutral and emotional expressions. These deficits are associated with changes in brain activation in the amygdala and the superior temporal sulcus (STS). However, until now there have been no studies that examined these different levels of social cognition and their neurobiological underpinnings in patients within one design. METHOD: Sixteen medicated schizophrenia out-patients and 16 matched healthy controls were studied with functional magnetic resonance imaging (fMRI) during a social cognition task that allows the investigation of affective ToM (aToM), emotion recognition and the processing of neutral facial expressions. RESULTS: Patients showed a deficit in emotion recognition and a more prominent deficit in aToM. The performance in aToM and in emotion recognition was correlated in the control group but not in the schizophrenia group. Region-of-interest analysis of functional brain imaging data revealed no difference between groups during aToM, but a hyperactivation in the schizophrenia group in the left amygdala and right STS during emotion recognition and the processing of neutral facial expressions. CONCLUSIONS: The results indicate that schizophrenia out-patients have deficits at several levels of social cognition and provide the first evidence that deficits on higher-order social cognitive processes in schizophrenia may be traced back to an aberrant processing of faces per se.

Bronchoscope insertion route and patient comfort during flexible bronchoscopy.

SETTING: Diagnostic flexible bronchoscopy performed in hospitalised and ambulatory patients in a tertiary care academic hospital in Monterrey, Mexico. OBJECTIVE: To determine the effect of the route of insertion of the bronchoscope (oral or nasal) on patient comfort, vocal cord visualisation, local anaesthetic and sedation requirements and possible complications. DESIGN: Prospective study carried out in patients aged ⩾ 18 years with an indication for flexible bronchoscopy. The route of insertion was randomly assigned. Symptoms related to the procedure were evaluated using a questionnaire. RESULTS: Sixty-three patients were included: 32 in the oral insertion group and 31 in the nasal insertion group. There was no statistically significant difference in patient discomfort (1.91 ± 2.95 vs. 2.39 ± 3.56 points on a scale of 1 to 10, P = 0.74) or procedural complications (4 vs. 0 events, P = 0.12) between study groups. Oral insertion was associated with less time to vocal cord visualisation (25.5 ± 156 s vs. 56 ± 61 s, P < 0.01), lower requirement for lidocaine (15 ± 7.50 vs. 16 ± 4 ml, P = 0.01) and fewer insertion failures (0 vs. 6 cases, P < 0.01). CONCLUSIONS: With intravenous sedoanalgesia, route of insertion did not affect patient comfort. However, the oral route was associated with faster vocal cord visualisation, less use of lidocaine and no insertion failure.

The influence of antipsychotic treatment on brain reward system reactivity in schizophrenia patients.

INTRODUCTION: Neuroleptic dysphoria is discussed as a serious side effect of antipsychotic medication. One aspect of this condition, a reduced motivation to reach potential rewards, might be induced by a blockade of striatal D2 receptors resulting in a reduced reactivity of the brain reward system. However, since this D2 antagonistic effect is higher for typical than atypical antipsychotics, typical antipsychotics should induce a stronger dampening of brain reward system activation. This hypothesis was tested in an event related functional magnetic resonance imaging study. METHODS: A monetary reward paradigm was presented to 30 schizophrenia patients, who were treated with typical or atypical antipsychotics or a combination of both. Hemodynamic responses were analyzed during the anticipation and the reception of the reward. RESULTS: Activation of the right ventral striatum, a core region of the brain reward system, was lower in patients treated with typical antipsychotics but only during the anticipation and not the delivery of a monetary reward. DISCUSSION: This result indicates that a D2 associated reduction of brain reward system reactivity might be the neurobiological correlate of reduced motivation observed in the context of neuroleptic dysphoria. Using typical antipsychotics might worsen this effect, increasing the negative symptomatology of schizophrenia patients.