Bipolar disorder is associated with significant social and occupational impairments, as well as increased risk for substance abuse and suicide. More research is needed to identify potential mechanisms associated with vulnerability to the disorder. Previous research has identified altered processing of emotional information in bipolar and bipolar-prone individuals, including attentional biases which appear to differ based on the current affective state of the individual. The current study applied a sensitive measure of attention (i.e., eye-tracking) to assess whether vulnerability to bipolar disorder, as indexed by hypomanic personality traits, would be correlated with biases in attention to emotional facial stimuli, independent of mood state. Hypomanic personality traits were hypothesized to be associated with greater attention to happy and angry faces, as indexed by faster initial orientation, more frequent gazes, and longer gaze duration for these stimuli. Participants completed self-report measures assessing current mood symptoms, positive and negative affect, and hypomanic personality traits. They then completed two tasks assessing attention for emotional faces. The first was an eye-tracking task, which measured latency to first fixation, total gaze duration and total number of gazes for each emotional face category. The second was a spatial cueing task which assessed both attentional engagement with emotional faces, and ability to disengage attention from this material. Hypomanic personality traits were significantly negatively correlated with latency to orient attention to happy faces. A trend toward decreased latency to orient to angry faces with higher hypomanic personality traits was also demonstrated. Hypomanic traits were not correlated with attention to sad faces. Furthermore, hypomanic traits were associated only with differences in initial orientation of attention, not with continued engagement or disengagement. The results of this study suggest that individuals with higher levels of hypomanic personality traits, who are hypothesized to be at greater risk of developing bipolar disorder, are characterized by differences in their initial orientation of attention to positive emotional stimuli, independent of their current mood state. This finding is indicative of biased information processing in individuals with vulnerability to bipolar disorder. Such a bias may have important clinical implications for individuals with a vulnerability to bipolar disorder, as it may represent a mechanism by which vulnerability leads to increased, and at times problematic, engagement with rewarding stimuli.

Underpinned by the Behavioural Approach System (BAS) dysregulation theory of bipolar disorder (BD), five studies were conducted in non-clinical samples to; refine the measurement of state Approach Motivation (AM); measure minor increases in AM; and then finally, to investigate how this relates to attentional biases for emotional stimuli. Study 1 attempted to clarify the phenomenology of state AM and revealed four separable factors that emerged from pooled AM questionnaire items. These structures loosely mapped on hypothesized components of the BAS (Depue & Iacono, 1989) that pertain to; cognitive elements of approach motivation (feeling determined and inspired); an energized, activated state; an affective structure relating to positive mood and outlook; and finally to feelings of excitement. Studies 2 and 3 investigated the validity of the four derived factors and their parent scales against a reward-oriented laboratory induction, a psychophysiological marker of AM, and a test of the discriminative power. The validity results suggested that the most well-established of the scales, the PANAS-PA, slightly outperformed the other measures by showing the greatest response to an AM induction. A second aim was to explore the substructure of a valid measure of mania risk - the hypomanic personality scale (HPS: Eckblad & Chapman, 1986) – in relation to AM responsivity. Unexpectedly, individuals who endorsed unpredictable and changeable moods (mood volatility) displayed elevated sympathetic arousal in response to control task. On this basis, and with a view to exploring the role selective attentional processes as a mediator of AM dysregulation that is relevant to bipolar disorder, study 4 and 5 utilised PANAS-PA to replicate a bi-directional congruency-effect found in the literature between elevations in AM and attentional information-processing biases to reward-related stimuli. Results in general did not support a causal influence of AM on attentional biases, nor did the attempted manipulation of attentional biases affect downstream AM. However, there was evidence that within a stratified sample of participants who reliably responded to the AM and control conditions, those at greater risk to mania exhibited an attentional bias for both positive and negative stimuli, relative those at lower risk to mania.

Sleep impairments are a hallmark of acute bipolar disorder (BD) episodes and are present even in the euthymic state. Studying healthy subjects who are vulnerable to BD can improve our understanding of whether sleep impairment is a predisposing factor. Therefore, we investigated whether vulnerability to BD, dimensionally assessed by the hypomanic personality scale (HPS), is associated with sleep disturbances in healthy subjects. We analyzed participants from a population-based cohort who had completed the HPS and had either a 7-day actigraphy recording or a Pittsburgh sleep quality index (PSQI) assessment. In addition, subjects had to be free of confounding diseases or medications. This resulted in 771 subjects for actigraphy and 1766 for PSQI analyses. We found strong evidence that higher HPS scores are associated with greater intraindividual sleep variability, more disturbed sleep and more daytime sleepiness. In addition, factor analyses revealed that core hypomanic features were especially associated with self-reported sleep impairments. Results support the assumption of disturbed sleep as a possibly predisposing factor for BD and suggest sleep improvement as a potential early prevention target.:I) Introduction ....................................................................................................... 3 II) Publication ..................................................................................................... 10 Supplementary Materials .................................................................................. 20 III) Summary ......................................................................................................... 37 IV) References ....................................................................................................... 42 V) Author contributions.......................................................................................... 45 VI) Declaration of authorship .................................................................................. 46 VII) Curriculum vitae ............................................................................................... 47 VIII) Publications ..................................................................................................... 48 IX) Acknowledgements ........................................................................................... 49

La désorganisation du discours est couramment observée en phase maniaque du trouble bipolaire. Elle peut se manifester par un langage incompréhensible, des idées décousues ou illogiques. Les premières études qui ont exploré les processus cognitifs sous-tendant ces perturbations du langage et du cours de la pensée dans le trouble bipolaire semblent en faveur de perturbations sémantiques. Pour déterminer la nature de ces perturbations, nous avons réalisé plusieurs études portant sur deux processus spécifiques : la propagation automatique de l’activation sémantique et l’inhibition sémantique. Pour évaluer ces processus nous avons construit deux tâches de décision lexicale basées sur l’amorçage sémantique. Celles-ci sont proposées à 17 patients bipolaires euthymiques ainsi qu’à un groupe de 61 personnes issues de la population générale pour lesquelles les traits de personnalité hypomaniaque et les tempéraments affectifs sont évalués. Les résultats montrent une moindre efficacité pour les deux processus dans le trouble bipolaire. Ces perturbations sont associées aux troubles du cours de la pensée. Dans la population générale, les résultats montrent que seule l’atteinte de la propagation automatique de l’activation est associée aux tempéraments hyperthymique et irritable. Cette association n’est pas retrouvée pour le processus d’inhibition sémantique, suggérant la mise en place de stratégies cognitives compensatoires lorsque les processus sont contrôlés. Nos résultats, associés à ceux de la littérature, semblent en faveur d’une approche dimensionnelle du trouble bipolaire et soulignent l’intérêt d’investiguer davantage la cognition dans les formes atténuées du trouble. / Disorganization of speech is commonly observed in the manic phase of bipolar disorder as incomprehensible language, disjointed or illogical ideas. Recent studies had explored the cognitive processes that underlie these disturbances of language and formal thought disorders in bipolar trouble. These studies appear to be in favor of semantic abnormalities. To determine the nature of these disturbances, we carried out studies which focus on two specific processes: the automatic spreading activation and the semantic inhibition. To assess these processes, two lexical decision tasks based on semantic priming were built. These tasks are proposed to 17 euthymic bipolar patients as well as to a group of 61 people from the general population for whom hypomanic personality traits and affective temperaments are evaluated. The results show lower efficacy for both processes in bipolar disorder. These disturbances are associated with the disturbances of formal thought disorders. In the general population, the results show that only the dysfunction of the automatic spreading activation is associated with hyperthymic and irritable temperaments. This association is not found for semantic inhibition, suggesting the intervention of compensatory cognitive strategies when the processes are controlled. Our results, combined with those of the literature, seem to be in favor of a dimensional approach to bipolar disorder and underline the interest of investigating cognition in the attenuated forms of the disorder.

Ce travail de thèse s’inscrit dans une approche dimensionnelle de la psychopathologie et son objectif est d’apporter de nouvelles connaissances au champ de recherche qui considère l’existence d’un continuum entre schizophrénie et trouble bipolaire ainsi qu’entre traits de personnalité et pathologies. Afin d’explorer ces continuums, nous avons étudié, grâce à la méthode des potentiels évoqués cognitifs et l’étude de certaines de leurs composantes (N400, LPC), les processus neurocognitifs sous-tendant l’intégration d’un contexte sémantique et sémantico-émotionnel dans la schizophrénie, le trouble bipolaire, les traits de personnalité schizotypique et les traits de personnalité hypomaniaque. Premièrement, nous avons montré, que les patients schizophrènes stabilisés et les patients bipolaires euthymiques présentent des patterns de modulation de la N400 différents lors de tâches impliquant l’intégration d’un contexte sémantique ou sémantico-émotionnel. Néanmoins, ces résultats en défaveur de l’existence d’un continuum entre schizophrénie et trouble bipolaire pourraient être la conséquence de l’absence de symptomatologie commune entre nos deux échantillons de patients. Deuxièmement, les résultats des études portant sur la population pathologique et ceux des études portant sur la population générale présentant des traits de personnalité semblent en faveur de l’existence d’un continuum entre population générale et pathologie. En effet, les personnes présentant des traits de personnalité hypomaniaque présentent des similitudes dans les atteintes des processus neurocognitifs sous-tendant l’intégration d’un contexte sémantique et sémantico-émotionnel avec les patients bipolaires, et les personnes présentant des traits de personnalité schizotypique présentent des similitudes dans les atteintes des processus neurocognitifs sous-tendant l’intégration d’un contexte sémantico-émotionnel avec les patients schizophrènes. L’ensemble de nos résultats associés à ceux de la littérature semblent en faveur d’une approche dimensionnelle de la psychopathologie bipolaire et schizophrénique où les symptômes, davantage que le diagnostic, doivent être envisagés comme le point central du continuum. / This work is part of a dimensional approach of the psychopathology. Its goal is to bring new knowledge to the field of research that considers the existence of a continuum between schizophrenia and bipolar disorder as well as between personality traits and pathologies. In order to explore these continuums, we have studied, thanks to event-related potential method and the study of N400 and LPC components, neurocognitive processes involved in the integration of semantic and semantico-emotional context in schizophrenia, bipolar disorder, schizotypal personality traits and hypomanic personality traits. We have first demonstrated that stabilized schizophrenic patients and euthymic bipolar patients have different patterns of the N400 modulation during tasks involving semantic and semantico-emotional integration. However, these results against the existence of a continuum between schizophrenia and bipolar disorder could be due to the lack of common symptoms in both samples. Secondly, the results of our studies dealing with clinical population and those dealing with general population with personality traits seem to be in favor to the existence of a continuum between general population and pathology. As a matter of fact individuals with hypomanic personality traits have similitude with bipolar patients in disturbance in neurocognitive processes involved in the integration of semantic and semantico-emotional context. Furthermore, individuals with schizotypal personality traits have common difficulties with schizophrenic patients in neurocognitive processes involved in semantico-emotional context integration. The results of our investigation, combined with those in the literature, are in favor of a dimensional approach of schizophrenic and bipolar psychopathology. And this approach is more about considering the symptoms as the central point of the continuum rather than the diagnostic.