Paul Roux

The emotional paradox: Dissociation between explicit and implicit processing of emotional prosody in schizophrenia

People with schizophrenia show well-replicated deficits on tasks of explicit recognition of emotional prosody. However it remains unclear whether they are still sensitive to the implicit cues of emotional prosody, particularly when they exhibit high levels of social anhedonia. A dual processing model suggesting a dissociation between the neural networks involved in explicit and implicit recognition of emotional prosody has yet to be validated. 21 participants with schizophrenia and 21 controls were recruited. In the explicit recognition task, individuals listened to semantically neutral words pronounced with two different emotions and judged their emotional prosody. In the vocal emotional Stroop task, patients and controls listened to words with a positive or negative emotional valence pronounced with congruent or incongruent emotional prosody and judged their emotional content. Patients were also assessed with the Chapman Anhedonia Questionnaire and the Schizophrenic Communication Disorders scale. Individuals with schizophrenia were impaired in their explicit recognition of emotional prosody related to controls. In contrast, they showed a vocal emotional Stroop effect that was identical to controls for reaction time and greater for accuracy: patients were still sensitive to implicit emotional prosody. In addition the vocal emotional Stroop score increased with social anhedonia but was unrelated to communication disorders. Whereas explicit vocal affect recognition is impaired, implicit processing of emotional prosody seems to be preserved in schizophrenia. Our results provide evidence that at a behavioural level, the implicit and explicit processing of emotional prosody can be dissociated. Remediation of emotional prosody recognition in schizophrenia should target cognitive rather than sensory processes.

Chronic Peripheral Inflammation is Associated With Cognitive Impairment in Schizophrenia: Results From the Multicentric FACE-SZ Dataset

OBJECTIVES Inflammation, measured by abnormal blood C-reactive protein (CRP) level, has been described in schizophrenia (SZ), being inconsistently related to impaired cognitive functions. The aim of the present study is to investigate cognitive impairment associated with abnormal CRP levels in a large multi-centric sample of community-dwelling SZ patients, using a comprehensive neuropsychological battery. METHOD Three hundred sixty-nine community-dwelling stable SZ subjects (76.2% men, mean age 32.7 y) were included and tested with a comprehensive battery of neuropsychological tests. Abnormal CRP level was defined as >3mg/L. RESULTS Multiple factor analysis revealed that abnormal CRP levels, found in 104 patients (28.2%), were associated with impaired General Intellectual Ability and Abstract Reasoning (aOR = 0.56, 95% CI 0.35-0.90, P = .014), independently of age, sex, education level, psychotic symptomatology, treatments, and addiction comorbidities. Abnormal CRP levels were also associated with the decline of all components of working memory (respectively effect size [ES] = 0.25, P = .033; ES = 0.27, P = .04; ES = 0.33, P = .006; and ES = 0.38, P = .004) and a wide range of other impaired cognitive functions, including memory (ES = 0.26, P = .026), learning abilities (ES = 0.28, P = .035), semantic memory (ES = 0.26, P = .026), mental flexibility (ES = 0.26, P = .044), visual attention (ES = 0.23, P = .004) and speed of processing (ES = 0.23, P = .043). CONCLUSION Our results suggest that abnormal CRP level is associated with cognitive impairment in SZ. Evaluating the effectiveness of neuroprotective anti-inflammatory strategies is needed in order to prevent cognitive impairment in SZ.

Kinematics matters: A new eye-tracking investigation of animated triangles

Eye movements have been recently recorded in participants watching animated triangles in short movies that normally evoke mentalizing (Frith–Happé animations). Authors have found systematic differences in oculomotor behaviour according to the degree of mental state attribution to these triangles: Participants made longer fixations and looked longer at intentional triangles than at triangles moving randomly. However, no study has yet explored kinematic characteristics of Frith–Happé animations and their influence on eye movements. In a first experiment, we have run a quantitative kinematic analysis of Frith–Happé animations and found that the time triangles spent moving and the distance between them decreased with the mentalistic complexity of their movements. In a second experiment, we have recorded eye movements in 17 participants watching Frith–Happé animations and found that some differences in fixation durations and in the proportion of gaze allocated to triangles between the different kinds of animations were entirely explained by low-level kinematic confounds. We finally present a new eye-tracking measure of visual attention, triangle pursuit duration, which does differentiate the different types of animations even after taking into account kinematic cofounds. However, some idiosyncratic kinematic properties of the Frith–Happé animations prevent an entirely satisfactory interpretation of these results. The different eye-tracking measures are interpreted as implicit and line measures of the processing of animate movements.

Cognitive profiles in euthymic patients with bipolar disorders: results from the FACE‐BD cohort

OBJECTIVES Although cognitive deficits are a well-established feature of bipolar disorders (BD), even during periods of euthymia, little is known about cognitive phenotype heterogeneity among patients with BD. METHODS We investigated neuropsychological performance in 258 euthymic patients with BD recruited via the French network of expert centers for BD. We used a test battery assessing six domains of cognition. Hierarchical cluster analysis of the cross-sectional data was used to determine the optimal number of subgroups and to assign each patient to a specific cognitive cluster. Subsequently, subjects from each cluster were compared on demographic, clinical functioning, and pharmacological variables. RESULTS A four-cluster solution was identified. The global cognitive performance was above normal in one cluster and below normal in another. The other two clusters had a near-normal cognitive performance, with above and below average verbal memory, respectively. Among the four clusters, significant differences were observed in estimated intelligence quotient and social functioning, which were lower for the low cognitive performers compared to the high cognitive performers. CONCLUSIONS These results confirm the existence of several distinct cognitive profiles in BD. Identification of these profiles may help to develop profile-specific cognitive remediation programs, which might improve functioning in BD.

Unsuppressible Repetition Suppression and exemplar-specific Expectation Suppression in the Fusiform Face Area

Recent work casts Repetition Suppression (RS), i.e. the reduced neural response to repeated stimuli, as the consequence of reduced surprise for repeated inputs. This research, along with other studies documenting Expectation Suppression, i.e. reduced responses to expected stimuli, emphasizes the role of expectations and predictive codes in perception. Here, we use fMRI to further characterize the nature of predictive signals in the human brain. Prior to scanning, participants were implicitly exposed to associations within face pairs. Critically, we found that this resulted in exemplar-specific Expectation Suppression in the fusiform face-sensitive area (FFA): individual faces that could be predicted from the associations elicited reduced FFA responses, as compared to unpredictable faces. Thus, predictive signals in the FFA are specific to face exemplars, and not only generic to the category of face stimuli. In addition, we show that under such circumstances, the occurrence of surprising repetitions did not trigger enhanced brain responses, as had been recently hypothesized, but still suppressed responses, suggesting that repetition suppression might be partly ‘unsuppressible’. Repetition effects cannot be fully modulated by expectations, which supports the recent view that expectation and repetition effects rest on partially independent mechanisms. Altogether, our study sheds light on the nature of expectation signals along the perceptual system.

Influence of Venus and Mars in the cognitive sky of schizophrenia. Results from the first-step national FACE-SZ cohort

OBJECTIVES Sex differences can yield important clues regarding illness pathophysiology and its treatment. Schizophrenia (SZ) has a lower incidence rate, and a better prognosis, in women versus men. The present study investigated the cognitive profiles of both sexes in a large multi-centre sample of community-dwelling SZ patients. METHOD 544 community-dwelling stable SZ subjects (141 women and 403 men; mean age 34.5±12.1 and 31.6±8.7years, respectively) were tested with a comprehensive battery of neuropsychological tests. RESULTS Although community-dwelling SZ men had more risk factors for impaired cognition (including first-generation antipsychotics administration and comorbid addictive disorders), women had lower scores on a wide range of cognitive functions, including current and premorbid intellectual functioning, working memory, semantic memory, non-verbal abstract thinking and aspects of visual exploration. However, women scored higher in tests of processing speed and verbal learning, as well as having a lower verbal learning bias. No sex difference were evident for visuospatial learning abilities, cued verbal recall, sustained attention and tests of executive functions, including cognitive flexibility, verbal abstract thinking, verbal fluency and planning abilities. CONCLUSION Sex differences are evident in the cognitive profiles of SZ patients. The impact on daily functioning and prognosis, as well as longitudinal trajectory, should be further investigated in the FACE-SZ follow-up study. Sex differences in cognition have implications for precision-medicine determined therapeutic strategies. LIMITS Given the restricted age range of the sample, future research will have to determine cognitive profiles across gender in late onset SZ.

Is the Questionnaire of Cognitive and Affective Empathy measuring two or five dimensions? Evidence in a French sample

Although many instruments measure empathy, most of them focus on specific facets (e.g., Spreng et al., 2009) or specific contexts (e.g. Wang et al., 2003) of empathy. For this reason, the Questionnaire of Cognitive and Affective Empathy (QCAE; Reniers et al., 2011) was recently built to grasp the general construct of empathy through its Affective-Cognitive duality, although not providing clear-cut results about the bidimensionality of the scale. In this study, Confirmatory Factor Analyses were conducted on the responses of 418 adults on the French QCAE (backtranslated for this study). A total of 8 models were tested - including the models of the original investigation. The 5-correlated factors model had the best fit, and the pattern of correlations between the factors did not support the Cognitive-Affective distinction. The QCAE is discussed as showing signs of psychometrical robustness, but also as a tool that is more 5-dimensional than bidimensional.

Cigarette smoking and schizophrenia: a specific clinical and therapeutic profile? Results from the FACE-Schizophrenia cohort

BACKGROUND Tobacco use is common in patients with schizophrenia (SZ) but little is known on the role of tobacco in the physiopathology or on the course of the disease. Only few studies embrace an extensive examination of clinical and therapeutic characteristics in stabilized patients. The objective of the present study was to determine the prevalence of tobacco smoking in stabilized SZ outpatients and the clinical and treatment characteristics associated with daily tobacco use in a large community-dwelling sample of patients. METHODS Three-hundred-and-sixty-one patients were included in the network of the FondaMental Expert Centers for Schizophrenia. Current tobacco status was self-declared. RESULTS 53.7% were smokers. Mean age at tobacco onset was 17.2years old. In multivariate analyses, after adjustment for confounding factors, positive symptoms and mean daily antipsychotic dose were associated with a higher frequency of tobacco use (OR=1.06 95%IC[1.02-1.12], for positive symptoms, OR=1.1, 95%IC[1.02-1.18] for daily antipsychotic dose). Education level, negative symptoms, anticholinergic agents, clozapine or aripiprazole administration were independently associated with a lower frequency of tobacco use (respectively OR=0.87, 95%IC [0.79, 0.95], OR=0.95, 95%IC[0.91-0.98], OR=0.41, 95%IC[0.22-0.76], OR=0.56, 95%IC=[0.32, 0.99] and OR=0.49, 95%IC [0.26-0.91]). CONCLUSION The prevalence of current tobacco smoking in a French community-dwelling SZ patients is higher that observed in the general population. Patients with tobacco use present clinical and therapeutic specificities that may involve interaction between cholinergic-nicotinic and dopaminergic systems. The present study suggests that some therapeutics may improve daily smoking behavior in smokers. These results should be confirmed in longitudinal studies.

Neuropsychological functioning, age, and medication adherence in bipolar disorder

Objectives Poor adherence to medication is frequent in bipolar disorder (BD) and has been associated with several factors. To date, the relationship between low adherence and neuropsychological functioning in BD is still unclear. As age and neuropsychological functioning might have opposing influences on adherence, our aim was to investigate this link with a particular focus on the effect of age. Methods In a cross-sectional study, we included 353 patients divided into two age-groups (16–46; 47–71) from a French cohort diagnosed with BD (type I, II, NOS) and strictly euthymic. All patients had a standardized clinical and neuropsychological assessment and were categorized as high (n = 186) or low (n = 167) adherent based on their score from the Medication Adherence Rating Scale. Clinical information was collected based on a standardized interview and clinical validated scales. Neuropsychological performances were evaluated with an established standardized neuropsychological battery for bipolar disorder patients. After univariate analysis, neuropsychological and clinical predictors of low adherence were included in two age-specific stepwise multiple logistic regressions. Results A smaller number of hospitalizations (OR = 0.846, p = 0.012), a shorter illness duration (OR = 0.937, p = 0.003) and higher adverse effects (OR = 1.082, p<0.001) were associated with a greater risk of low adherence in the younger patients. In the older patients, low adherence was also predicted by a smaller number of hospitalizations (OR = 0.727, p = 0.008) and higher adverse effects (OR = 1.124, p = 0.005). Interestingly poor inhibition performance was also a significant predictor of low adherence in older patients (OR = 0.924, p = 0.030). Conclusions We found an age-specific relationship between cognitive functioning and adherence in patients with BD. Poor inhibition performances predicted low adherence in older patients only. Our results highlight the need to provide age-adapted therapeutic interventions to improve adherence in patients with BD.

Systematic prevention of severe constipation induced by antipsychotic agents: A quasi-experimental study.

Constipation is a frequent, potentially life-threatening sideeffect of both first and second generation antipsychotic agents (De Hert et al., 2011). For instance, patients receiving clozapine have a 70-fold higher death rate from severe constipation than from agranulocytosis (Cohen et al., 2012). Although recent reviews advocate for a systematic prevention (Sagy et al., 2014), available evidence regarding cost-effective strategies is sparse. The present quasiexperimental study compared the occurrence of severe constipation in a psychiatric intensive care unit before and after the implementation of a preventive protocol. Lowdose macrogol 3350 (2–6 bags of 13.8 g per day) was proposed as first-line preventive treatment to all patients receiving antipsychotic agents. Whenever the patient experienced a 48-h period without defecation, one rectal delivery of sterculia gum was used as second-line treatment to prevent severe constipation. The preventive protocol was implemented in mid-june 2014. Data regarding antipsychotic agents and laxatives actually received by all consecutive patients hospitalized from mid-june 2013 to mid-june 2014 (period 1) and from mid-june 2014 to mid-june 2015 (period 2) were collected from computerized records (Pharmas software, Computer Engineering, Paris). Our endpoint was severe constipation as identified by the use of high-dose macrogol 3350 (118 g in 2 l of water taken in 2 h), a treatment routinely used in our unit as medical treatment for severe constipation. Associations between period, drugs and severe constipation were tested with two-sided chi-square tests. The study protocol followed Declaration of Helsinki guidelines. From period 1 to period 2, the use of first-line and second-line laxatives increased from 27.7% to 63.9% and from 9.1% to 13.2%, respectively. Only 4 cases of severe constipation were recorded in 101 stays (3.3%) during period 2 compared to 10 cases in 122 stays (9.9%) during period 1 (χ=4.118, P=0.042). Restricting our analyses to patients who actually received first-line laxatives magnified the strength of this association (5.1% versus 28.6%, χ=11.279,