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 towards 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 signalling. In addiction models, activity of the KOR is potentiated by stressors and critically controls drug-seeking and relapse. In depression paradigms, KOR signalling 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 behavioural dysregulation and increased risk for distinct but interacting psychopathologies.

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.

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.