The current study utilized structural equation modeling (SEM) to examine the factor-to-factor relations and temporal associations between disturbances in negative affect (NA) and positive symptoms of psychosis (PP). Data were drawn from a large, public-domain data set (MacArthur Violence Risk Assessment Study). A dimensional approach was used to conceptualize and identify latent variables of NA (depression, anxiety, and guilt) and PP (hallucinations, delusions, and thought disorder) among individuals with a diagnosis of primary psychotic disorder. Results showed that anxiety, guilt, and depressed mood modeled an NA latent variable, and that hallucinations and unusual thought content modeled a PP latent variable. As predicted, results revealed strong, significant cross-sectional (synchronous) associations between NA and PP at each measured time-frame, suggesting that NA and PP occurred concurrently within the sample. Contrary to predictions, no significant cross-lagged effect between NA and PP was identified (10 weeks and 20 weeks respectively).

The purpose of the present study was to examine the effects of positive and negative symptoms, and duration of illness on emotion processes / ability to understand emotion related cues, experience of emotion, and expression of emotion. A total of 46 schizophrenia patients from Ankara Oncology Hospital Psychiatry Clinic / 23 of them were diagnosed with schizophrenia for at least 10 years, and 23 of them were diagnosed for less than 10 years, participated in the study. Besides, a total of 23 non-clinical subjects / which were similar to the clinical group in terms of educational information, participated to the study. A video-clip which consists of scenes that elicited four types of emotions (fear, disgust, sadness, happiness) was presented to the participants. Understanding of emotion related cues and the experienced emotion were rated through self-report. Facial expressions of the participants were rated through their recorded faces by three psychologists, who were specifically trained for emotional facial expression rating. Symptomatology was assessed by Positive and Negative Symptom Scale (PANSS), and Calgary Depression Scale for schizophrenia patients. Presence of any psychopathology of healthy group was measured through Brief Symptom Inventory. Multivariate Analysis of Variance (MANOVA) revealed that chronic patients presented more understanding of context impairments than acute patients and non-clinical group. In addition to these findings, positive symptoms assessed by PANSS were found to be positively correlated with the understanding context impairment. Therefore, It was suggested that positive symptoms, such as hallucinations and delusions interfere with understanding context task. The results were discussed in the light of the literature and clinical and research implications of the study presented. Finally, necessity of using neurological, biological and cognitive assessment methods for further studies was suggested in order to understand deficits in emotional processes.

Résumé : Depuis la caractérisation de la schizophrénie, les cliniciens ont noté une sensibilité anormale à la douleur chez leurs patients. D’un autre côté, la littérature publiée sur le sujet est plutôt inconsistante concernant la nature du changement de douleur rapportée. Dans un effort pour mieux caractériser le profil de réponse à la douleur dans la schizophrénie, nous avons donné des stimulations nociceptives aiguës et prolongées (à répétition rapide; sommation temporelle) à des patients souffrant de schizophrénie et à des sujets sains. En mesurant le score de douleur subjective et la réponse du réflexe de flexion nociceptif en réponse à des stimulations électriques transcutanées, il a été possible d’évaluer la contribution des circuits spinaux à la douleur chez les patients et les sujets sains. Les résultats révèlent une sensibilité augmentée à la douleur aiguë chez les patients atteints de schizophrénie (i.e., un seuil de détection de la douleur plus bas que les sujets sains) mais aussi une diminution de la sommation temporelle de la douleur quand les stimuli se répètent fréquemment. Les différences intergroupes dans l’expérience subjective à la douleur n’étaient pas accompagnées d’une différence dans l’amplitude du réflexe nociceptif, suggérant ainsi une origine supra-spinale du phénomène observé. Il est intéressant de noter que les symptômes positifs de la schizophrénie étaient corrélés négativement avec les scores de seuil de douleur chez les patients atteints de schizophrénie, suggérant que les distorsions de la pensée et des fonctions peuvent être reliées à une augmentation de la sensibilité à la douleur aiguë dans la schizophrénie. Ces résultats suggèrent la présence d’un profil de sensibilité à la douleur unique chez les patients atteints de schizophrénie ayant des répercussions importantes pour les pratiques cliniques. // Abstract : Ever since the characterization of schizophrenia, clinicians have noted abnormal pain sensitivity in their patients. The published literature, however, is inconsistent concerning the nature of the change reported. In an effort to better characterize the pain response profile of schizophrenia patients, we provided both acute and prolonged (i.e., rapidly-repeating: temporal summation) painful stimuli to schizophrenia patients and healthy controls. By measuring subjective pain ratings and nociceptive flexion reflexes in response to transcutaneous electrical stimulations of the sural nerve, it was possible to evaluate the contribution of spinal circuits to pain in patients and controls. Results revealed increased sensitivity to acute pain in schizophrenia patients (i.e., lower pain detection thresholds for schizophrenia patients than for controls), but decreased temporal summation of pain when painful stimuli repeated frquently. Group differences in subjective experience were not accompanied by group differences in nociceptive flexion reflex activity, suggesting supra-spinal origins to the change in pain experienced by patients. Interestingly, positive symptoms correlated negatively with pain threshold values among patients, suggesting that distortions of thought and function relate to pain sensitivity in schizophrenia. These results indicate the presence of a unique pain response profile for schizophrenia patients which have important implications for clinical practice.

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Computational modelling has been gaining an increasing amount of support from the neuroscience community as a tool to assay cognition and computational processes in the brain. Lately, scientists have started to apply computational methods from neuroscience to the study of psychiatry to gain further insight into the mechanisms leading to mental disorders. In fact, only recently has psychiatry started to move away from categorising illnesses using behavioural symptoms in an attempt for a more biologically driven diagnosis. To date, several neurobiological anomalies have been found in schizophrenia and led to a multitude of conceptual framework attempting to link the biology to the patients’ symptoms. Computational modelling can be applied to formalise these conceptual frameworks in an effort to test the validity or likelihood of each hypothesis. Recently, a novel conceptual model has been proposed to describe how positive symptoms (delusions, hallucinations and thought disorder) and cognitive symptoms (poor decision-making, i.e. “executive functioning”) might arise in schizophrenia. This framework however, has not been tested experimentally or against computational models. The focus of this thesis was to use a combination of behavioural experiments and computational models to independently assess the validity of each component that make up this framework. The first study of this thesis focused on the computational analysis of a disrupted prediction-error signalling and its implications for decision-making performances in complex tasks. Briefly, we used a reinforcement-learning model of a gambling task in rodents and disrupted the prediction-error signal known to be critical for learning. We found that this disruption can account for poor performances in decision-making due to an incorrect acquisition of the model of the world. This study illustrates how disruptions in prediction-error signalling (known to be present in schizophrenia) can lead to the acquisition of an incorrect world model which can lead to poor executive functioning or false beliefs (delusions) as seen in patients. The second study presented in this thesis addressed spatial working memory performances in chronic schizophrenia, bipolar disorder, first episode psychosis and family relatives of DISC1 translocation carriers. We build a probabilistic inference model to solve the working memory task optimally and then implemented various alterations of this model to test commonly debated hypotheses of cognitive deficiency in schizophrenia. Our goal was to find which of these hypotheses accounts best for the poor performance observed in patients. We found that while the performance at the task was significantly different for most patients groups in comparison to controls, this effect disappeared after controlling for IQ in one group. The models were nonetheless fitted to the experimental data and suggest that working memory maintenance is most likely to account for the poor performances observed in patients. We propose that the maintenance of information in working memory might have indirect implications for measures of general cognitive performance, as these rely on a correct filtering of information against distractions and cortical noise. Finally the third study presented in this thesis assessed the performance of medicated chronic schizophrenia patients in a statistical learning task of visual stimuli and measured how the acquired statistics influenced their perception. We find that patient with chronic schizophrenia appear to be unimpaired at statistical learning of visual stimuli. The acquired statistics however appear to induce less expectation-driven ‘hallucinations’ of the stimuli in the patients group than in controls. We find that this is in line with previous literature showing that patients are less susceptible to expectation-driven illusions than controls. This study highlights however the idea that perceptual processes during sensory integration diverge from this of healthy controls. In conclusion, this thesis suggests that impairments in reinforcement learning and Bayesian inference appear to be able to account for the positive and cognitive symptoms observed in schizophrenia, but that further work is required to merge these findings. Specifically, while our studies addressed individual components such as associative learning, working memory, implicit learning & perceptual inference, we cannot conclude that deficits of reinforcement learning and Bayesian inference can collectively account for symptoms in schizophrenia. We argue however that the studies presented in this thesis provided evidence that impairments of reinforcement learning and Bayesian inference are compatible with the emergence of positive and cognitive symptoms in schizophrenia.

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