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...