Comorbidity is a major issue in psychiatry that notably associates with more severe symptoms, longer illness duration, and higher service utilization. Therefore, identifying key clusters of comorbidity and exploring the underlying pathophysiological mechanisms represent important steps toward improving mental health care. In the present review, we focus on the frequent association between addiction and depression. In particular, we summarize the large body of evidence from preclinical models indicating that the kappa opioid receptor (KOR), a member of the opioid neuromodulatory system, represents a central player in the regulation of both reward and mood processes. Current data suggest that the KOR modulates overlapping neuronal networks linking brainstem monoaminergic nuclei with forebrain limbic structures. Rewarding properties of both drugs of abuse and natural stimuli, as well as the neurobiological effects of stressful experiences, strongly interact at the level of KOR signaling. In addiction models, activity of the KOR is potentiated by stressors and critically controls drug-seeking and relapse. In depression paradigms, KOR signaling is responsive to a variety of stressors, and mediates despair-like responses. Altogether, the KOR represents a prototypical substrate of comorbidity, whereby life experiences converge upon common brain mechanisms to trigger behavioral dysregulation and increased risk for distinct but interacting psychopathologies.

Les effets psychologiques de l'isolement ont déjà été décrits dans la littérature (expéditions polaires, sous-marins, prison). Néanmoins l'échelle du confinement mis en oeuvre à l'occasion de la pandémie à COVID-19 est inédite. Il nous faut non seulement relire les études publiées, mais aussi anticiper les problèmes psychologiques qui pourraient survenir pendant ou à distance du confinement. Nous avons fait le choix d'aller au-delà de la littérature COVID-19 pour examiner les implications des conséquences connues du confinement : l'ennui, l'isolement social, le stress, le manque de sommeil. L'anxiété, le trouble de stress post-traumatique, la dépression et les conduites suicidaires, les conduites addictives, les violences domestiques sont des effets décrits du confinement, mais les mécanismes d'émergence de ces troubles et leurs interrelations restent à étudier. Par exemple, quels sont les mécanismes d'émergence du trouble de post-traumatique dans le cadre du confinement ? Nous rappelons aussi les points de vigilance à garder sur des conséquences telles que les troubles des conduites alimentaires, les hallucinations, curieusement ignorées dans la littérature sur le confinement, alors qu'une vaste littérature fait le lien entre isolement social et hallucinations. Du fait de conséquences psychopathologiques larges, il nous faut partir à la recherche des différents symptômes pour permettre leur prise en charge. Nous résumons rapidement les approches diagnostiques et thérapeutiques déjà mises en place, comme la télémédecine, qui connaît un développement rapide à l'occasion de la crise du COVID-19. AbstractThe psychological effects of isolation have already been described in the literature (polar expeditions, submarines, prison). Nevertheless, the scale of confinement implemented during the COVID-19 pandemic is unprecedented. In addition to reviewing the published studies, we need to anticipate the psychological problems that could arise during or at a distance from confinement. We have gone beyond the COVID-19 literature in order to examine the implications of the known consequences of confinement, like boredom, social isolation, stress, or sleep deprivation. Anxiety, post-traumatic stress disorder, depression, suicidal or addictive behaviours, domestic violence are described effects of confinement, but the mechanisms of emergence of these disorders and their interrelationships remain to be studied. For example, what are the mechanisms of emergence of post-traumatic stress disorders in the context of confinement? We also remind the reader of points of vigilance to be kept in mind with regard to eating disorders and hallucinations. Hallucinations are curiously ignored in the literature on confinement, whereas a vast literature links social isolation and hallucinations. As with domestic violence, we need to look for these symptoms in order to enable management. Due to the broad psychopathological consequences, we have to look for these various symptoms to manage them. We quickly summarize the diagnostic and therapeutic...

Patients with schizophrenia display an impaired sense of temporal continuity, and we showed that they judge events as being simultaneous even in case of large onset asynchronies. We check here whether this means a fusion of events in time, or on the contrary, a segregation of events and a deficit in coding time-event structure. Subjects decided whether 2 squares were displayed simultaneously or asynchronously on the screen and gave their response by hitting a left or right response key. The implicit processing of asynchrony was explored by means of the Simon effect, which refers to the finding that manual responses are biased to the side of the stimulus. We checked whether responses were biased to the side of the first or second square, when squares were asynchronous and displayed on opposite sides. Results revealed an enlarged time window in patients irrespective of the squares' position (intra- vs interhemispheric presentation). But for asynchronies eliciting "synchronous" judgments, patients' responses were biased to the side of the first square. In contrast, controls were biased in all cases to the side of the second square. The inverse effects observed below thresholds in patients and controls cannot be attributed to a generalized deficit. In controls, elementary predictive mechanisms would allow anticipation of upcoming events, whereas patients appear to process squares as if isolated rather than following each other. Predictive mechanisms would be impaired in patients, who would rather rely on reactive mechanisms in order to perceive asynchrony.

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Clinical observations suggest that the experience of time phenomenology is disturbed in schizophrenia, possibly originating disorders in dynamic cognitive functions such as language or motor planning. We examined the subjective evaluation of temporal structure using an experimental approach involving judgments of simultaneity of simple, visually presented stimuli. We included a priming procedure, ie, a subthreshold presentation of simultaneous or asynchronous stimuli. This allowed us to evaluate the effects of subthreshold synchrony and to check for bias effects, ie, changes in the criteria used by the subjects to rate the stimuli. Primes were adapted to the responses of the subjects. Bias effects were thus expected to yield a change in the efficiency of the prime and to induce a change in the amplitude of the priming effect. Nineteen outpatients with schizophrenia and their individually matched controls participated in the study. In all tests, patients required longer delays between stimuli to detect that they were asynchronous. In other words, they judged stimuli to be synchronous even when their onset was separated by delays of 100 milliseconds and even more in some cases. These results contrasted with preserved effects of subthreshold synchrony. Our findings argue against the hypothesis that the patients' responses were influenced by biases. We conclude that the subjective evaluation of simultaneity/asynchrony is impaired in schizophrenia, thus leading to impairment in the phenomenology of event-structure coding. The method used in the present study provides a novel approach to the assessment of those disturbances related to time in patients with schizophrenia.

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We review studies suggesting time disorders on both automatic and subjective levels in patients with schizophrenia. Patients have difficulty explicitly discriminating between simultaneous and asynchronous events, and ordering events in time. We discuss the relationship between these difficulties and impairments on a more elementary level. We showed that for undetectable stimulus onset asynchronies below 20 ms, neither patients nor controls merge events in time, as previously believed. On the contrary, subjects implicitly distinguish between events even when evaluating them to be simultaneous. Furthermore, controls privilege the last stimulus, whereas patients seem to stay stuck on the first stimulus when asynchronies are sub-threshold. Combining previous results shows this to be true for patients even for asynchronies as short as 8 ms. Moreover, this peculiarity predicts difficulties with detecting asynchronies longer than 50 ms, suggesting an impact on the conscious ability to time events. Difficulties on the subjective level are also correlated with clinical disorganization. The results are interpreted within the framework of predictive coding which can account for an implicit ability to update events. These results complement a range of other results, by suggesting a difficulty with binding information in time as well as space, and by showing that information processing lacks continuity and stability in patients. The time perspective may help bridge the gap between cognitive impairments and clinical symptoms, by showing how the innermost structure of thought and experience is disrupted.