Sleep Biomarkers, Health Comorbidities, and Neurocognition in Obstructive Sleep Apnea.

OBJECTIVES: Obstructive sleep apnea (OSA) is associated with cognitive impairment but the relationships between specific biomarkers and neurocognitive domains remain unclear. The present study examined the influence of common health comorbidities on these relationships. Adults with suspected OSA (N=60; 53% male; M age=52 years; SD=14) underwent neuropsychological evaluation before baseline polysomnography (PSG). Apneic syndrome severity, hypoxic strain, and sleep architecture disturbance were assessed through PSG. METHODS: Depression (Center for Epidemiological Studies Depression Scale, CESD), pain, and medical comorbidity (Charlson Comorbidity Index) were measured via questionnaires. Processing speed, attention, vigilance, memory, executive functioning, and motor dexterity were evaluated with cognitive testing. A winnowing approach identified 9 potential moderation models comprised of a correlated PSG variable, comorbid health factor, and cognitive performance. RESULTS: Regression analyses identified one significant moderation model: average blood oxygen saturation (AVO2) and depression predicting recall memory, accounting for 31% of the performance variance, p<.001. Depression was a significant predictor of recall memory, p<.001, but AVO2 was not a significant predictor. The interaction between depression and AVO2 was significant, accounting for an additional 10% of the variance, p<.001. The relationship between low AVO2 and low recall memory performance emerged when depression severity ratings approached a previously established clinical cutoff score (CESD=16). CONCLUSIONS: This study examined sleep biomarkers with specific neurocognitive functions among individuals with suspected OSA. Findings revealed that depression burden uniquely influence this pathophysiological relationship, which may aid clinical management. (JINS, 2018, 28, 864-875).

Dose-dependent cannabis use, depressive symptoms, and FAAH genotype predict sleep quality in emerging adults: a pilot study.

BACKGROUND: Cannabis has been shown to affect sleep in humans. Findings from animal studies indicate that higher endocannabinoid levels promote sleep, suggesting that chronic use of cannabis, which downregulates endocannabinoid activity, may disrupt sleep. OBJECTIVES: This study sought to determine if past-year cannabis use and genes that regulate endocannabinoid signaling, FAAH rs324420 and CNR1 rs2180619, predicted sleep quality. As depression has been previously associated with both cannabis and sleep, the secondary aim was to determine if depressive symptoms moderated or mediated these relationships. METHODS: Data were collected from 41 emerging adult (ages 18-25) cannabis users. Exclusion criteria included Axis I disorders (besides SUD) and medical and neurologic disorders. Relationships were tested using multiple regressions, controlling for demographic variables, past-year substance use, and length of cannabis abstinence. RESULTS: Greater past-year cannabis use and FAAH C/C genotype were associated with poorer sleep quality. CNR1 genotype did not significantly predict sleep quality. Depressive symptoms moderated the relationship between cannabis use and sleep at a nonsignificant trend level, such that participants with the higher cannabis use and depressive symptoms reported the more impaired sleep. Depressive symptoms mediated the relationship between FAAH genotype and sleep quality. CONCLUSIONS: This study demonstrates a dose-dependent relationship between chronic cannabis use and reported sleep quality, independent of abstinence length. Furthermore, it provides novel evidence that depressive symptoms mediate the relationship between FAAH genotype and sleep quality in humans. These findings suggest potential targets to impact sleep disruptions in cannabis users.

Abnormal cortical gyrification in criminal psychopathy.

Background: Psychopathy is a personality disorder characterized by interpersonal and emotional abnormalities (e.g., lack of empathy and guilt) and antisocial behavior. Psychopathy has been associated with a number of structural brain abnormalities, most notably in orbital frontal and anterior/medial temporal regions, that may underlie psychopathic individuals' problematic behaviors. Past research evaluating cortical structure in psychopathy has considered thickness and volume, but to date no study has investigated differences in cortical gyrification, a measure of cortical complexity thought to reflect early neurodevelopmental cortical connectivity. Methods: We measured the local gyrification index (LGI) in a sample of 716 adult male inmates and performed a whole brain analysis assessing the relationship between LGI and total and factor scores on the Hare Psychopathy Checklist-Revised (PCL-R). Results: PCL-R scores were negatively associated with LGI measures within the right hemisphere in the midcingulate cortex (MCC) and adjacent regions of the superior frontal gyrus as well as lateral superior parietal cortex. Additionally, PCL-R Factor 1 scores (interpersonal/affective traits) predicted less LGI within the right MCC and adjacent dorsomedial frontal cortex and greater LGI in bilateral occipital cortex. Scores on PCL-R Factor 2, indicating impulsivity and antisocial behaviors, did not predict LGI in any regions. Conclusions: These findings suggest that psychopathy, particularly the interpersonal and affective traits, are associated with specific structural abnormalities that form during neurodevelopment and these abnormalities may underlie aberrant brain functioning in regions important in emotional processing and cognitive control.

Poorer frontolimbic white matter integrity is associated with chronic cannabis use, FAAH genotype, and increased depressive and apathy symptoms in adolescents and young adults.

BACKGROUND: The heaviest period of cannabis use coincides with ongoing white matter (WM) maturation. Further, cannabis-related changes may be moderated by FAAH genotype (rs324420). We examined the association between cannabis use and FAAH genotype on frontolimbic WM integrity in adolescents and emerging adults. We then tested whether observed WM abnormalities were linked with depressive or apathy symptoms. METHODS: Participants included 37 cannabis users and 37 healthy controls (33 female; ages 18-25). Multiple regressions examined the independent and interactive effects of variables on WM integrity. RESULTS: Regular cannabis users demonstrated reduced WM integrity in the bilateral uncinate fasciculus (UNC) (MD, right: p = .009 and left: p = .009; FA, right: p = .04 and left: p = .03) and forceps minor (fMinor) (MD, p = .03) compared to healthy controls. Marginally reduced WM integrity in the cannabis users was found in the left anterior thalamic radiation (ATR) (FA, p = .08). Cannabis group ∗ FAAH genotype interaction predicted WM integrity in bilateral ATR (FA, right: p = .05 and left: p = .001) and fMinor (FA, p = .02). In cannabis users, poorer WM integrity was correlated with increased symptoms of depression and apathy in bilateral ATR and UNC. CONCLUSIONS: Consistent with prior findings, cannabis use was associated with reduced frontolimbic WM integrity. WM integrity was also moderated by FAAH genotype, in that cannabis-using FAAH C/C carriers and A carrying controls had reduced WM integrity compared to control C/C carriers. Observed frontolimbic white matter abnormalities were linked with increased depressive and apathy symptoms in the cannabis users.

Impact of cannabis use on prefrontal and parietal cortex gyrification and surface area in adolescents and emerging adults.

BACKGROUND: Regions undergoing maturation with CB1 receptors may be at increased risk for cannabis-induced alterations. Here, we examine the relationships between cannabis use and prefrontal (PFC) and inferior parietal gyrification and surface area (SA) in youth. METHODS: Participants included 33 cannabis users and 35 controls (ages 18-25). Exclusions included co-morbid psychiatric/neurologic disorders and heavy other drug use. Multiple regressions and Pearson r correlations examined the effects of cannabis use on gyrification, SA and cognition. RESULTS: Cannabis use was associated with decreased gyrification in: ventral-medial PFC (RH: [FDR corrected p=.02], LH: [FDR corrected p=.02]); medial PFC (RH: [FDR corrected p=.02], LH: [FDR corrected p=.02]); and frontal poles (RH: [FDR corrected p=.02], LH: [FDR corrected p=.02]). No differences were observed in bilateral hemispheres, PFC, dorsolateral, ventrolateral, or inferior parietal ROIs. Cannabis use was associated with marginally decreased SA in left: medial PFC [FDR corrected p=.09], and ventral lateral PFC: [FDR corrected p=.09]. In cannabis users, increased gyrification was associated with improved working-memory performance in right medial (p=.003), ventral-medial (p=.03), and frontal pole ROIs (p=.007). CONCLUSIONS: Cannabis use was associated with reduced gyrification in PFC regions implicated in self-referential thought and social cognition. Results suggest that these gyrification characteristics may have cognitive implications.

5-HTTLPR Genotype Moderates the Effects of Past Ecstasy Use on Verbal Memory Performance in Adolescent and Emerging Adults: A Pilot Study.

OBJECTIVE: Ecstasy use is associated with memory deficits. Serotonin transporter gene (5-HTTLPR) polymorphisms have been linked with memory function in healthy samples. The present pilot study investigated the influence of 5-HTTLPR polymorphisms on memory performance in ecstasy users, marijuana-using controls, and non-drug-using controls, after a minimum of 7 days of abstinence. METHOD: Data were collected from 116 young adults (18-25 years-old), including 45 controls, 42 marijuana users, and 29 ecstasy users, and were balanced for 5-HTTLPR genotype. Participants were abstinent seven days prior to completing memory testing. Three MANCOVAs and one ANCOVA were run to examine whether drug group, 5-HTTLPR genotype, and their interactions predicted verbal and visual memory after controlling for gender, past year alcohol use, other drug use, and nicotine cotinine levels. RESULTS: MANCOVA and ANCOVA analysis revealed a significant interaction between drug group and genotype (p = .03) such that ecstasy users with the L/L genotype performed significantly worse on CVLT-2 total recall (p = .05), short (p = .008) and long delay free recall (p = .01), and recognition (p = .006), with the reverse pattern found in controls. Ecstasy did not significantly predict visual memory. 5-HTTLPR genotype significantly predicted memory for faces (p = .02); short allele carriers performed better than those with L/L genotype. CONCLUSIONS: 5-HTTLPR genotype moderated the effects of ecstasy on verbal memory, with L/L carriers performing worse compared to controls. Future research should continue to examine individual differences in ecstasy's impact on neurocognitive performance as well as relationships with neuronal structure. Additional screening and prevention efforts focused on adolescents and emerging adults are necessary to prevent ecstasy consumption.