Social cognition is commonly altered in people with psychosis. Two main brain networks have been implicated: the default-mode network (DMN), which is associated with socio-cognitive processing, and the salience network (SN) associated with socio-affective processing. Disturbances to the resting-state functional connectivity of these networks have been identified in schizophrenia and high-risk individuals, but there have been no studies in adolescents displaying distinct trajectories of subclinical psychotic-like experiences (PLEs). To address this, the present study measured SN and DMN resting-state connectivity in a unique longitudinally followed sample of youth (n = 92) presenting with typical and atypical 4-year PLE trajectories. Compared to the typically developing low PLE control group, the atypical increasing PLE trajectory displayed reduced connectivity between the SN and DMN, increased connectivity between left and right insula, and widespread dysconnectivity from the insula and amygdala. These alterations are similar to those reported in schizophrenia and clinical high-risk samples, suggesting that early detection may be useful for mapping the developmental trajectories of psychotic disorders.

Adolescence is a key period for neurocognitive maturation where deviation from normal developmental trajectories may be tied to adverse mental health outcomes. Cognitive disruptions have been noted in populations at risk for psychosis and are known to accompany periods of sleep deprivation. This study aims to assess the role of cognition as a mediator between sleep disruptions and psychosis risk. A cohort of 3801 high school students (51% female, mean age = 12.8, SD = 0.45 years) was recruited from 31 Montreal high schools. Measures of sleep, psychotic-like experiences, inhibition, working memory, perceptual reasoning, and delayed recall were collected from participants on a yearly basis over the five years of their high school education. A multi-level model mediation analysis was performed controlling for sex and time squared. Response inhibition was shown to be associated with, and to mediate (B = -0.005, SD = 0.003, p = 0.005*) the relationship between sleep disruptions (B = -0.011, SD = 0.004, p < 0.001*) and psychotic-like experiences (B = 0.411, SD = 0.170, p = 0.005*). Spatial working memory deficits on a given year were associated with a higher frequency of psychotic-like experiences that same year (B = -0.046, SD = 0.018, p = 0.005*) and the following year (B = -0.051, SD = 0.023, p = 0.010*), but were not associated with sleep disturbances. No significant associations were found between our variables of interest and either delayed recall or perceptual reasoning at the within person level. Findings from this large longitudinal study provide evidence that the association between sleep disruptions and psychosis risk is specifically mediated by inhibitory rather than general cognitive impairments. The association of spatial working memory, response inhibition, and sleep disruptions with psychotic-like experiences suggests that these factors may represent potential targets for preventative interventions.

Objectives Increasing evidence implicates cannabis consumption as a key risk factor in the development of psychosis, but the mechanisms underpinning this relationship remain understudied. This study proposes to determine whether sleep disruption acts as a mediator of the cannabis-to-psychosis relationship.Study Design This longitudinal study assessed measures of cannabis use frequency, sleep quality (SQ), and psychotic-like experiences (PLEs) were collected using self-reported questionnaires. Data were collected from September 2012 to September 2018. Data were collected from a general population sample of adolescents who entered the seventh grade in 31 schools in the Greater Montreal area. The study uses data collected on an annual basis from 3801 high school students from grades 7 to 11. The aforementioned measures were measured using the Detection of Alcohol and Drug Problems in Adolescents questionnaire, a SQ Likert scale, and measures the Psychotic-Like Experiences Questionnaire for Children.Study Results Results show a reciprocal 1-year cross-lagged effect of cannabis use and sleep (beta = -0.076, 95% CI = -0.037 to -0.018, P = .000), of sleep on cannabis use (beta = -.016, 95% CI = -0.025 to -0.006, P = .007), of sleep on PLEs (beta = -0.077, 95%CI = -0.014 to -0.051, P = .000), and of PLEs on sleep (beta = -0.027, 95% CI = -0.037 to -0.018, P = .000). We additionally found a 2 years indirect lagged-effect of cannabis use on PLEs (beta = 0.068, 95% CI = 0.024 to 0.113, P = .011) mediated by 1-year sleep (beta = 0.006, 95% CI = 0.003 to 0.009, P = .001).Conclusions Our results suggest sleep disruptions simultaneously aggravate, and are aggravated by, cannabis addiction and PLEs. The longitudinal sleep-mediated effect of cannabis use on PLEs encourages further research into the role of sleep as a potential therapeutic target in the prevention of cannabis-related psychosis.

BACKGROUND:Impairment in cognition is frequently associated with acute ketamine administration. However, some questions remain unanswered as to which deficits are most prominent and what variables modulate these effects.METHODS:A literature search yielded 56 experimental studies of acute ketamine administration that assessed cognition in 1041 healthy volunteers. A multivariate meta-analysis was performed, and effect sizes were estimated for eleven cognitive domains: attention, executive function, response inhibition, social cognition, speed of processing, verbal / language, verbal learning, verbal memory, visual learning & memory, visuospatial abilities, and working memory.RESULTS:There were small-to-moderate impairments across all cognitive domains. Deficits in verbal learning / memory were most prominent, whereas response inhibition was the least affected. Meta-regression analysis revealed that the negative effects of ketamine on cognition are dependent on infusion dose and plasma level, but unaffected by enantiomer type, route of administration, sex or age. A publication bias was observed.DISCUSSION:Acute ketamine broadly impairs cognition across all domains among healthy individuals. Verbal learning and memory figures most prominently in cognitive impairment elicited by acute ketamine administration.

Self-disturbances constitute a hallmark of psychosis, but it remains unclear whether these alterations are present in at-risk populations, and therefore their role in the development of psychosis has yet to be confirmed. The present study addressed this question by measuring neural correlates of self-other processing in youth belonging to three developmental trajectories of psychotic experiences. Eighty-six youths were recruited from a longitudinal cohort of over 3800 adolescents based on their trajectories of Psychotic-Like Experiences from 12 to 16 years of age. Participants underwent neuroimaging at 17 years of age (mean). A functional neuroimaging task evaluating self- and other-related trait judgments was used to measure whole-brain activation and connectivity. Youth who showed an increasing trajectory displayed hypoactivation of the dorsomedial prefrontal cortex and hypoconnectivity with the cerebellum. By contrast, youth who showed a decreasing trajectory displayed decreased activation of the superior temporal gyrus, the inferior frontal gyrus, and the middle occipital gyrus. These findings suggest that the increasing trajectory is associated with alterations that might erode distinctions between self and other, influencing the emergence of symptoms such as hallucinations. The decreasing trajectory, in comparison, was associated with hypoactivations in areas influencing attention and basic information processing more generally. These alterations might affect the trajectories’ susceptibilities to positive vs. negative symptoms, respectively.

The aim of this study was to investigate the neural bases of facial emotion processing before the onset of clinical psychotic symptoms in youth belonging to well-defined developmental trajectories of psychotic-like experiences (PLEs). A unique sample of 86 youths was recruited from a population-based sample of over 3800 adolescents who had been followed from 13 to 17 years of age. Three groups were identified based on validated developmental trajectories: a control trajectory with low and decreasing PLEs, and two atypical trajectories with moderate to elevated baseline PLEs that subsequently decreased or increased. All had functional magnetic resonance imaging data collected during a facial emotion processing task. Functional activation and connectivity data were analyzed for different contrasts. The increasing PLE trajectory displayed more positive psychotic symptoms while the decreasing trajectory exhibited more negative symptoms relative to the control group. During face processing, both atypical trajectories displayed decreased activations of the right inferior frontal gyrus (IFG), while the increasing trajectory displayed a negative signal in the precentral gyrus. The increasing PLE trajectory also displayed impaired connectivity between the amygdala, ventromedial prefrontal cortex, and cerebellum, and between the IFG, precuneus, and temporal regions, while the decreasing trajectory exhibited reduced connectivity between the amygdala and visual regions during emotion processing. Both atypical PLE trajectories displayed alterations in brain regions involved in attention salience. While the increasing trajectory with more positive symptoms exhibited dysconnectivity in areas that influence emotion salience and face perception, the decreasing trajectory with more negative symptoms had impairments in visual information integration areas. These group-specific features might account for the differential symptom expression.

BACKGROUND:Impairment in cognition is frequently associated with acute cannabis consumption. However, some questions remain unanswered as to which deficits are most prominent and which demographic groups are most vulnerable.METHODS:A literature search yielded 52 experimental studies of acute administration of partial CB1 receptor agonists (i.e. cannabis, THC, and nabilone) that assessed cognitive dysfunction in 1580 healthy volunteers. Effect size estimates were calculated using the Comprehensive Meta-Analysis for the following six cognitive domains: attention, executive functions, impulsivity, speed of processing, verbal learning/memory, and working memory.RESULTS:There were small-to-moderate impairments across all cognitive domains. Deficits in verbal learning/memory and working memory were more prominent, whereas attention and impulsivity were the least affected. Meta-regression analysis revealed that the greater the male ratio is in a sample, the greater the negative effect of cannabinoids on speed of processing and impulsivity. Analysis of route of administration showed that the deficits in speed of processing were smaller in the oral, relative to smoking, vaping, and intravenous administration studies. A publication bias was observed.DISCUSSION:Verbal learning/memory and working memory are most prominently affected by acute administration of partial CB1 receptor agonists. The results are consistent with the residual cognitive effects that have been documented among chronic cannabis users.

Background The endogenous cannabinoid system mediates the psychoactive effects of cannabis in the brain. It has been argued that this system may play a key role in the pathophysiology of schizophrenia. While some studies have consistently shown that the levels of anandamide, an endogenous cannabinoid ligand, are increased in the cerebrospinal fluid of schizophrenia patients, inconsistent results have been observed in studies measuring anandamide levels in the periphery. Here, we sought to determine if the assessment of peripheral anandamide levels in patients evaluated in a psychiatric emergency setting would show robust increases. Methods One hundred seven patients with a schizophrenia-spectrum disorder from the psychiatric emergency settings of the Institut Universitaire en Santé Mentale de Montréal and 36 healthy volunteers were included in the study. A subsample of thirty patients were assessed at two time points: at the emergency and at their discharge from the hospital. Anxious and depressive symptoms, sleep and substance use were assessed using self-report questionnaires. In addition to anandamide, the levels of oleoylethanolamide (OEA), an anorexigenic fatty-acid ethanolamide, were also measured, since the prevalence of the metabolic syndrome is increased in schizophrenia. Plasma levels of anandamide and OEA were measured using liquid chromatography and mass spectrometry. Results Plasma anandamide and OEA levels were significantly increased in schizophrenia patients, relative to controls (Cohen’s d=1.0 and 0.5, respectively). Between-group differences remained significant after controlling for metabolic measures. No differences were observed between schizophrenia patients with and without a comorbid substance use disorder at baseline. Importantly, the levels of both endocannabinoids significantly decreased after discharge from the emergency setting. Conclusion The current results add to the growing body of evidence of endocannabinoid alterations in schizophrenia. The strong elevation of plasma anandamide levels in schizophrenia patients assessed in the psychiatric emergency setting suggests that anandamide and OEA area potential biomarkers of the psychological turmoil associated with this context.