استفاده از کانابیس با حافظه هیجانی بهتر در اسکیزوفرنی همراه است: یک مطالعه تصویربرداری رزونانس مغناطیسی عملکردی

In schizophrenia cannabis abuse/dependence is associated with poor compliance and psychotic relapse. Despite this, the reasons for cannabis abuse remain elusive, but emotions may play a critical role in this comorbidity. Accordingly, we performed a functional magnetic resonance imaging study of emotional memory in schizophrenia patients with cannabis abuse (dual-diagnosis, DD). Participants comprised 14 DD patients, 14 non-abusing schizophrenia patients (SCZ), and 21 healthy controls (HC) who had to recognize positive and negative pictures while being scanned. Recognition of positive and negative emotions was prominently impaired in SCZ patients, relative to HC, while differences between DD and HC were smaller. For positive and negative stimuli, we observed significant activations in frontal, limbic, temporal and occipital regions in HC; in frontal, limbic and temporal regions in DD; and in temporal, parietal, limbic and occipital regions in the SCZ group. Our results suggest that emotional memory and prefrontal lobe functioning are preserved in DD relative to SCZ patients. These results are consistent with previous findings showing that cannabis abuse is associated with fewer negative symptoms and better cognitive functioning in schizophrenia. Longitudinal studies will need to determine whether the relative preservation of emotional memory is primary or secondary to cannabis abuse in schizophrenia.

Regier et al., 1990 and Cantor-Graae et al., 2001). In decreasing order, schizophrenia patients abuse alcohol, cannabis, and stimulants, if we exclude tobacco (Regier et al., 1990). Drug preferences are influenced by sample age. Indeed, a recent meta-analysis by Koskinen et al. (2010) reported that alcohol use disorder was more common in older schizophrenia populations, while younger patients (<30 years) more frequently suffered from cannabis use disorder (lifetime risk up to 45%). As other psychoactive substance, cannabis negatively interferes with the course and treatment of schizophrenia. Cannabis abuse/dependence is indeed associated with higher psychotic relapses and hospitalization rates, more severe positive symptoms, non-adherence to antipsychotic therapy, an earlier age of schizophrenia onset, as well as more suicide attempts (Cantor-Graae et al., 2001, Dervaux et al., 2003, Zammit et al., 2008 and Foti et al., 2010). Despite these debilitating consequences, the reasons motivating cannabis smoking in schizophrenia remain elusive. Preliminary evidence suggests that emotions may play a role in this comorbidity. For instance, a study by Kirkpatrick et al. (1996) showed that the deficit syndrome of schizophrenia (presence of primary, prominent and enduring negative symptoms) is associated with lower rates of lifetime SUD. Moreover, two recent meta-analyses by our group underlined that relative to non-addicted schizophrenia patients, those dependent on cannabis express fewer negative symptoms, including anhedonia and blunting of affect (Potvin et al., 2006), and that they experience more severe depressive symptoms (Potvin et al., 2007a). Consistently, the most frequently reported reasons for substance use in schizophrenia are to experience a high and to cope with stress, anxiety and dysphoria (Green et al., 2004 and Dekker et al., 2009). In a complementary fashion, other investigations have shown that cannabis abuse/dependence is associated with better pre-morbid adjustment levels and better social skills in schizophrenia (Arndt et al., 1992, Salyers and Mueser, 2001 and Yucel et al., 2012). Whether these differences are the cause or the consequence of substance abuse in schizophrenia remains a matter of debate. One way or another, mounting evidence suggests that there are significant emotional differences between schizophrenia patients with and without cannabis smoking, and that these emotional differences contribute to their use of cannabis. Altogether, these observations have led Blanchard et al., 1999 and Blanchard et al., 2000 to hypothesize that schizophrenia patients use psychoactive substances (including cannabis) in order to regulate their emotions. To our knowledge, no study has examined the neural correlates of emotional experience in schizophrenia patients with substance abuse, apart from two previous studies by our group. This is of major concern given that approximately half of schizophrenia patients struggle with lifetime SUD, particularly cannabis use disorders, for which the median lifetime rate was 27.1% in the meta-analysis of Koskinen et al. (2010). Our preliminary studies addressed this question by investigating negative emotion processing between schizophrenia patients with and without SUD (Mancini-Marie et al., 2006 and Potvin et al., 2007a). The results of both studies suggest a preserved functioning of the medial prefrontal cortex in dual-diagnosis patients compared to non-addicted schizophrenia patients. Nevertheless, these studies presented certain limitations that we aimed to address in the current study: (1) the inclusion of dual-diagnosis patients abusing mixed substances (cannabis and/or alcohol), (2) the lack of a control group of healthy subjects, (3) the restricted use of negatively charged stimuli, and finally (4) the specific investigation of emotion experience. Reliable evidence suggests that there are significant deficits in facial affect identification in schizophrenia, and that emotional expression is flattened in these patients ( Tremeau, 2006 and Kohler et al., 2010). By contrast, numerous experimental studies have examined emotional experience in schizophreni through the use of images and videos, and a recent synthesis of this literature has revealed subtle, if any, differences in the reported experience of emotion in schizophrenia patients compared to controls ( Kring and Caponigro, 2010). This pattern of findings is inconsistent with the flattening of affect and anhedonia observed by raters during psychiatric interviews ( Kring and Caponigro, 2010). As a means of explaining this discrepancy between laboratory and clinical settings, some authors relied on the vast literature documenting significant explicit memory impairments in schizophrenia ( Leavitt and Goldberg, 2009) to propose that this disorder may be associated with impairments in recalling (not experiencing) emotional events, and to propose that this may explain why patients seem emotionally indifferent in clinical settings ( Kring and Moran, 2008). Therefore, our group decided to specifically examine the memory of emotional stimuli in schizophrenia, and its neural correlates. Behaviorally, most studies that have looked at emotional memory tasks have reported poorer performances of schizophrenia patients relative to controls ( Sergerie et al., 2010, Becerril and Barch, 2011 and Lakis et al., 2011). As for neuroimaging findings, the limited literature in schizophrenia displayed reduced brain activations in dorsolateral prefrontal cortex, hippocampus and amygdala during the recall of emotional stimuli ( Whalley et al., 2009, Sergerie et al., 2010, Becerril and Barch, 2011, Lakis et al., 2011 and Wolf et al., 2011). Thus, the aim of the present study was to investigate the neural correlates of emotional memory in schizophrenia patients with and without cannabis use disorder, relative to healthy participants. We opted to investigate the memory of negative (sad, fearful, disgusting) and positive (agreeable, happy) stimuli, which are both part of our everyday experiences. We expected to observe an increased emotional experience and better recognition accuracy of both negative and positive material in dual-diagnosis patients compared to non-abusing schizophrenia patients. Generally, in terms of cerebral functions, we envisaged that dual-diagnosis patients would present a more typical pattern of brain activations for both conditions relative to non-abusing schizophrenia patients; that is, greater activations of the limbic system and prefrontal cortex.