Association between continued cannabis use during pregnancy and symptoms of anxiety and depression.

Cannabis use in pregnancy is common, as are mental health disorders, but the association between the two is not well established. This study is a single-site retrospective cohort. Urine testing for cannabis was evaluated at two-time points to categorize women as having never used, quit or continued to use. Edinburgh Postnatal Depression Scale (EPDS) and Generalized Anxiety Disorder (GAD) screen results were compared across groups using multinomial logistic regression. In addition, EPDS and GAD change scores between initiation of care and delivery were analyzed. 604 women were included, 221 (36.3%) with positive toxicology testing for cannabis at the initiation of care. Women who continued cannabis use were significantly more likely to have elevated GAD and EPDS scores (2.55 [1.31, 4.99]) and EPDS score (2.75 [1.43, 5.28]), respectively as compared to those with no use. No significant differences were found between groups in GAD or EPDS change scores t women with higher depression scores on the EPDS had 2.70 times the odds of being in the continuous use group compared to the quit using group (aOR = 2.70, 95% CI = [1.30, 5.88]). Both anxiety and depression symptoms were found to be associated with cannabis use and continued use during pregnancy.

Conscious and unconscious brain responses to food and cocaine cues.

Visual presentation of appetitive and negative cues triggers fast responses in the human brain. Here we assessed functional MRI (fMRI) responses to food, cocaine, and neutral cues presented at a subliminal ("unconscious", 33 ms) and supraliminal ("conscious", 750 and 3000 ms) level in healthy, cocaine naïve volunteers. Because there is evidence of circadian variability in reward sensitivity, our second aim was to assess diurnal variability in the brain's reactivity to cues. Sixteen participants completed two randomly ordered fMRI sessions (once 9-11 AM and another 5-7 PM). in which food, cocaine, and neutral cues were presented for 33, 750 and 3000 ms. Participants rated food cues as positive and "wanted" (more so in evenings than mornings), and cocaine cues as negative (no diurnal differences). fMRI showed occipital cortex activation for food>neutral, cocaine>neutral and cocaine>food; dorsolateral prefrontal cortex for cocaine>neutral and cocaine>food, and midbrain for cocaine>food (all pFWE < 0.05). When comparing unconscious (33 ms) > conscious (750 and 3000 ms) presentations, we observed significant differences for cocaine>neutral and cocaine>food in occipital cortex, for cocaine>neutral in the insula/temporal lobe, and for food>neutral in the middle temporal gyrus (pFWE < 0.05). No diurnal differences for brain activations were observed. We interpret these findings to suggest that negative items (e.g., cocaine) might be perceived at a faster speed than positive ones (e.g., food), although we cannot rule out that the higher saliency of cocaine cues, which would be novel to non-drug using individuals, contributed to the faster speed of detection.

Association Between Reduced Brain Glucose Metabolism and Cortical Thickness in Alcoholics: Evidence of Neurotoxicity.

BACKGROUND: Excessive alcohol consumption is associated with reduced cortical thickness (CT) and lower cerebral metabolic rate of glucose (CMRGlu), but the correlation between these 2 measures has not been investigated. METHODS: We tested the association between CT and cerebral CMRGlu in 19 participants with alcohol use disorder (AUD) and 20 healthy controls. Participants underwent 2-Deoxy-2-[18F]fluoroglucose positron emission tomography to map CMRGlu and magnetic resonance imaging to assess CT. RESULTS: Although performance accuracy on a broad range of cognitive domains did not differ significantly between AUD and HC, AUD had widespread decreases in CT and CMRGlu. CMRGlu, normalized to cerebellum (rCMRGlu), showed significant correlation with CT across participants. Although there were large group differences in CMRGlu (>17%) and CT (>6%) in medial orbitofrontal and BA 47, the superior parietal cortex showed large reductions in CMRGlu (~17%) and minimal CT differences (~2.2%). Though total lifetime alcohol (TLA) was associated with CT and rCMRGlu, the causal mediation analysis revealed significant direct effects of TLA on rCMRGlu but not on CT, and there were no significant mediation effects of TLA, CT, and rCMRGlu. CONCLUSIONS: The significant correlation between decrements in CT and CMRGlu across AUD participants is suggestive of alcohol-induced neurotoxicity, whereas the findings that the most metabolically affected regions in AUD had minimal atrophy and vice versa indicates that changes in CT and CMRGlu reflect distinct responses to alcohol across brain regions.

Cannabis Addiction and the Brain: a Review.

(©Zehra A, Liuck, Manza P, Wiers CE, Volkow ND Wergh J, 2018. Reprinted with permission from Journal of Neuroimmune Pharmacology (2018) 13:438-452).

Apparent diffusion coefficient changes in human brain during sleep - Does it inform on the existence of a glymphatic system?

The role of sleep in brain physiology is poorly understood. Recently rodent studies have shown that the glymphatic system clears waste products from brain more efficiently during sleep compared to wakefulness due to the expansion of the interstitial fluid space facilitating entry of cerebrospinal fluid (CSF) into the brain. Here, we studied water diffusivity in the brain during sleep and awake conditions, hypothesizing that an increase in water diffusivity during sleep would occur concomitantly with an expansion of CSF volume - an effect that we predicted based on preclinical findings would be most prominent in cerebellum. We used MRI to measure slow and fast components of the apparent diffusion coefficient (ADC) of water in the brain in 50 healthy participants, in 30 of whom we compared awake versus sleep conditions and in 20 of whom we compared rested-wakefulness versus wakefulness following one night of sleep-deprivation. Sleep compared to wakefulness was associated with increases in slow-ADC in cerebellum and left temporal pole and with decreases in fast-ADC in thalamus, insula, parahippocampus and striatal regions, and the density of sleep arousals was inversely associated with ADC changes. The CSF volume was also increased during sleep and was associated with sleep-induced changes in ADCs in cerebellum. There were no differences in ADCs with wakefulness following sleep deprivation compared to rested-wakefulness. Although we hypothesized increases in ADC with sleep, our findings uncovered both increases in slow ADC (mostly in cerebellum) as well as decreases in fast ADC, which could reflect the distinct biological significance of fast- and slow-ADC values in relation to sleep. While preliminary, our findings suggest a more complex sleep-related glymphatic function in the human brain compared to rodents. On the other hand, our findings of sleep-induced changes in CSF volume provide preliminary evidence that is consistent with a glymphatic transport process in the human brain.

Neural correlates of visual attention in alcohol use disorder.

Numerous studies have documented cognitive impairments in multiple domains in patients with an alcohol use disorder (AUD), including perceptuomotor, executive, and visuospatial functions. Although the neural underpinnings of cognitive deficits in AUD have been studied extensively, the neural basis of attention deficits in AUD remains relatively unexplored. Here, we investigated neural responses to a visual attention task (VAT) in 19 recently abstinent patients with AUD and 23 healthy control participants (HC) using functional MRI (fMRI). AUD had a mean number of 62 ± 34SD drinks per week and 29 ± 13 years' history of alcohol use. Results show that there were no behavioral differences (accuracy or reaction time) between groups during the VAT. For both groups, the VAT activated brain areas associated with visual attention load (i.e., parietal and prefrontal cortices) and visual processing (i.e., occipital cortex), which is in line with previous reports on the same task in healthy volunteers. Despite similar behavioral performances, AUD participants showed decreased VAT activation in regions of the dorsal and ventral attention networks, including parietal and prefrontal cortices, and in the insula as compared to controls. These findings corroborate differences in attention networks in AUD compared to HC that might underlie attention deficits in AUD, whereas impairments in the insula could reflect a disruption of interoception processing as found in other addictions.

Emotion Recognition Biases in Alcohol Use Disorder.

BACKGROUND: Alcohol use disorder (AUD) has been associated with impairments in cognitive and emotional function, including difficulty identifying emotional facial expressions. However, it is unclear whether these deficits are associated with alcohol consumption or related anxious and depressive symptoms. METHODS: We compared the recognition of emotional faces expressing happiness, surprise, sadness, fear, anger, and disgust in 19 AUD participants and 19 healthy volunteers using the Cambridge Neuropsychological Test Automated Battery Emotion Recognition Task. We analyzed group differences in response latency, accuracy, and misidentification patterns (as defined by the tendency to mislabel facial expressions as exhibiting specific emotions). To assess whether misidentification patterns were associated with drinking severity, we also examined associations with alcohol consumption over the past 90 days. RESULTS: There were no differences in response latency or accuracy between groups. However, there were group differences in misidentification patterns. While controls tended to misidentify emotional expressions as happy, those with AUD tended to misidentify expressions as angry or disgusted. In AUD participants, the degree to which individuals were biased toward anger or disgust was positively correlated with the number of drinks they consumed in the past 90 days but was not associated with depression or anxiety scores. CONCLUSIONS: Our findings suggest that individuals with AUD have a bias toward misidentifying emotional facial expressions as hostile, which is not mediated by associated mood changes. This provides further evidence of disrupted social cognition in AUD.

Methylation of the dopamine transporter gene in blood is associated with striatal dopamine transporter availability in ADHD: A preliminary study.

Dopamine transporters (DAT) are implicated in the pathogenesis and treatment of attention-deficit hyperactivity disorder (ADHD) and are upregulated by chronic treatment with methylphenidate, commonly prescribed for ADHD. Methylation of the DAT1 gene in brain and blood has been associated with DAT expression in rodents' brains. Here we tested the association between methylation of the DAT1 promoter derived from blood and DAT availability in the striatum of unmedicated ADHD adult participants and in that of healthy age-matched controls (HC) using Positron Emission Tomography (PET) and [11 C]cocaine. Results showed no between-group differences in DAT1 promoter methylation or striatal DAT availability. However, the degree of methylation in the promoter region of DAT1 correlated negatively with DAT availability in caudate in ADHD participants only. DAT availability in VS correlated with inattention scores in ADHD participants. We verified in a postmortem cohort with ADHD diagnosis and without, that DAT1 promoter methylation in peripheral blood correlated positively with DAT1 promoter methylation extracted from substantia nigra (SN) in both groups. In the cohort without ADHD diagnosis, DAT1 gene expression in SN further correlated positively with DAT protein expression in caudate; however, the sample size of the cohort with ADHD was insufficient to investigate DAT1 and DAT expression levels. Overall, these findings suggest that peripheral DAT1 promoter methylation may be predictive of striatal DAT availability in adults with ADHD. Due to the small sample size, more work is needed to validate whether DAT1 methylation in blood predicts DAT1 methylation in SN in ADHD and controls.

Influence of alcoholism and cholesterol on TSPO binding in brain: PET [11C]PBR28 studies in humans and rodents.

Neuroinflammation appears to contribute to neurotoxicity observed with heavy alcohol consumption. To assess whether chronic alcohol results in neuroinflammation we used PET and [11C]PBR28, a ligand that binds to the 18-kDa translocator protein (TSPO), to compare participants with an alcohol use disorder (AUD: n = 19) with healthy controls (HC: n = 17), and alcohol-dependent (n = 9) with -nondependent rats (n = 10). Because TSPO is implicated in cholesterol's transport for steroidogenesis, we investigated whether plasma cholesterol levels influenced [11C]PBR28 binding. [11C]PBR28 binding did not differ between AUD and HC. However, when separating by TSPO genotype rs6971, we showed that medium-affinity binders AUD participants showed lower [11C]PBR28 binding than HC in regions of interest (whole brain, gray and white matter, hippocampus, and thalamus), but no group differences were observed in high-affinity binders. Cholesterol levels inversely correlated with brain [11C]PBR28 binding in combined groups, due to a correlation in AUD participants. In rodents, we observed no differences in brain [11C]PBR28 uptake between alcohol-dependent and -nondependent rats. These findings, which are consistent with two previous [11C]PBR28 PET studies, may indicate lower activation of microglia in AUD, whereas failure to observe alcohol effects in the rodent model indicate that species differences do not explain the discrepancy with prior rodent autoradiographic studies reporting increases in TSPO binding with chronic alcohol. However, reduced binding in AUD participants could also reflect competition from endogenous TSPO ligands such as cholesterol; and since the rs6971 polymorphism affects the cholesterol-binding domain of TSPO this could explain why differences were observed only in medium-affinity binders.

Impact of sugar on the body, brain, and behavior.

Sugar is highly palatable and rewarding, both in its taste and nutritive input. Excessive sugar consumption, however, may trigger neuroadaptations in the reward system that decouple eating behavior from caloric needs and leads to compulsive overeating. Excessive sugar intake is in turn associated with adverse health conditions, including obesity, metabolic syndrome, and inflammatory diseases. This review aims to use recent evidence to connect sugar's impact on the body, brain, and behavior to elucidate how and why sugar consumption has been implicated in addictive behaviors and poor health outcomes.

ß-Amyloid accumulation in the human brain after one night of sleep deprivation.

The effects of acute sleep deprivation on ß-amyloid (Aß) clearance in the human brain have not been documented. Here we used PET and 18F-florbetaben to measure brain Aß burden (ABB) in 20 healthy controls tested after a night of rested sleep (baseline) and after a night of sleep deprivation. We show that one night of sleep deprivation, relative to baseline, resulted in a significant increase in Aß burden in the right hippocampus and thalamus. These increases were associated with mood worsening following sleep deprivation, but were not related to the genetic risk (APOE genotype) for Alzheimer's disease. Additionally, baseline ABB in a range of subcortical regions and the precuneus was inversely associated with reported night sleep hours. APOE genotyping was also linked to subcortical ABB, suggesting that different Alzheimer's disease risk factors might independently affect ABB in nearby brain regions. In summary, our findings show adverse effects of one-night sleep deprivation on brain ABB and expand on prior findings of higher Aß accumulation with chronic less sleep.

Cannabis Addiction and the Brain: a Review.

Cannabis is the most commonly used substance of abuse in the United States after alcohol and tobacco. With a recent increase in the rates of cannabis use disorder (CUD) and a decrease in the perceived risk of cannabis use, it is imperative to assess the addictive potential of cannabis. Here we evaluate cannabis use through the neurobiological model of addiction proposed by Koob and Volkow. The model proposes that repeated substance abuse drives neurobiological changes in the brain that can be separated into three distinct stages, each of which perpetuates the cycle of addiction. Here we review previous research on the acute and long-term effects of cannabis use on the brain and behavior, and find that the three-stage framework of addiction applies to CUD in a manner similar to other drugs of abuse, albeit with some slight differences. These findings highlight the urgent need to conduct research that elucidates specific neurobiological changes associated with CUD in humans.