The role of sleep in the link between cannabis use and memory function: evidence from a cross-sectional study.

Background: It is known that cannabis use affects memory and sleep problems independently. However, to date, how memory and sleep problems may interact as a result of cannabis use remains unknown.Objectives: We performed a secondary analysis of existing data to determine whether sleep quality mediates the association between cannabis use and memory and whether sex moderated these effects.Methods: A total of 141 adults with cannabis use disorder (CUD) (83 men) and 87 without CUD (39 men) participated in this study. Outcome measures included self-reported sleep problems from the past 7 days (Marijuana Withdrawal Checklist), learning and memory performance via the short visual object learning task (sVOLT), short visual object learning task delayed (sVOLTd), and verbal memory via the N-back. Bootstrapped mediation and moderated mediation analyses were run to test if sleep quality mediated the association between cannabis use and memory outcomes and whether sex moderated these effects, respectively.Results: Sleep quality mediated the effect of group (i.e. adults with and without CUD) on sVOLT efficiency scores (indirect effect ß = -.08, 95% CI [-0.14, -0.04]) and sVOLTd efficiency scores (indirect effect ß = -.09, 95% CI [-0.14, -0.04]), where greater sleep difficulties was associated with poorer memory performance (decreased efficiency scores). Sex did not moderate these relationships.Conclusion: These initial findings of a mediating role of sleep in the association between CUD and visual learning memory highlight potential critical downstream effects of disrupted sleep in those with CUD and suggest the importance of investigating sleep in CUD.

The contributions of the endocannabinoid system and stress on the neural processing of reward stimuli.

The brain's endocannabinoid system plays a crucial role in reward processes by mediating appetitive learning and encoding the reinforcing properties of substances. Evidence also suggests that endocannabinoids are an important constituent of neuronal substrates involved in emotional responses to stress. Thus, it is critical to understand how the endocannabinoid system and stress may affect reward processes given their importance in substance use disorders. We examined the relationship between factors that regulate endocannabinoid system signaling (i.e., cannabinoid receptor genes and prolonged cannabis exposure) and stress on fMRI BOLD response to reward cues using multivariate statistical analysis. We found that proxies for endocannabinoid system signaling (i.e., endocannabinoid genes and chronic exposure to cannabis) and stress have differential effects on neural response to cannabis cues. Specifically, a single nucleotide polymorphism (SNP) variant in the cannabinoid receptor 1 (CNR1) gene, early life stress, and current perceived stress modulated reward responsivity in long-term, heavy cannabis users, while a variant in the fatty acid amide hydrolase (FAAH) gene and current perceived stress modulated cue-elicited response in non-using controls. These associations were related to distinct neural responses to cannabis-related cues compared to natural reward cues. Understanding the contributions of endocannabinoid system factors and stress that lead to downstream effects on neural mechanisms underlying sensitivity to rewards, such as cannabis, will contribute towards a better understanding of endocannabinoid-targeted therapies as well as individual risks for cannabis use disorder.

Negative symptoms of familial schizophrenia breed true in unstable (vs. stable) cerebral-ventricle pedigrees.

A pattern of negative symptoms associated with a high rate of ongoing brain and ventricular instability has been described in a cohort of schizophrenia spectrum probands (patients with schizophrenia, schizoaffective disorder depressed and bipolar, and psychosis NOS) (Garver, D.L., Nair, T.R., Christensen, J.D., Holcomb, J., Ramberg, J., Kingsbury, S., 1999. Differential patterns of premorbid functioning, symptoms and neuroleptic response in stable and unstable ventricular-volume schizophrenia. Neuropsychopharmacology 20, in press). The present study contrasts the prevalence of negative symptoms in first- and second-degree relatives of probands with unstable ventricle volume (UnsVV) and stable ventricle volume (SVV). One hundred and sixteen first- and second-degree relatives of 10 probands were interviewed using the SANS, the 'Characterization of Course: "Pattern of Symptoms"' [from Comprehensive Assessment of Symptoms and History (CASH)], SCID and SCID-II by interviewers blind to the status of the proband. Thirty-five of the 116 family members met DSM-IV criteria for schizophrenia, SA depressed, 'Cluster A' of the SCID-II (paranoid, schizotypal, schizoid personality disorder), psychosis NOS, or psychotic affective disorder. These 35 family members were defined as falling within a 'schizophrenia spectrum' as described by Farmer, A.E., McGuffin, P., Gottesman, I.I., 1987. Arch. Gen. Psychiatry 44, 634-641, but with the addition of DSM-IV affective psychosis. On that basis, the 35 members were considered 'affected family members' (AFMs). The remaining 81 family members were considered unaffected. The 'predominant symptoms of illness' (during the past 2-3 years) for 25 of the 35 AFMs could be characterized according to the 'Patterns of Symptoms' derived from the CASH. Twenty-five of the 35 AFMs were found to maintain a predominant symptom pattern during the course of illness, which could be characterized according to the 'Pattern of Symptoms' as 'predominantly positive' or 'predominantly negative'. Three of the probands had UnsVV; seven had SVV. Of the 35 AFMs, 11 were related to the UnsVV probands, and 24 were relatives of the SVV probands. The nine rated AFMs of the UnsVV probands showed a trend toward higher SANS scores (7.3 +/- 5.1) (mean +/- s.d.) than the 20 rated AFMs of SVV probands (4.3 +/- 5.1) (p = 0.08) at the time of the interview. Eighty-three per cent (eight of 10) of rated affected pedigree members of the pedigrees delineated by probands with UnsVV probands had a predominantly negative symptom course of illness, and 96% (23 of 24) of rated affected pedigree members of the pedigrees with SVV probands had a predominantly positive symptom course of illness during the preceding 2-3 years (p = 0.002). None of the 12 rated affected pedigree members within pedigrees having UnsVV probands were married at the time of the interview; 45% (14 of 31) of affected pedigree members having SVV probands were married (p = 0.004). A psychiatric disorder, characterized by unstable cerebral ventricles and predominant negative symptoms (including avoidance/failure of marital relationships) appears symptomatically to breed true in pedigrees containing schizophrenia-like illnesses.