Intrinsic Frontolimbic Connectivity and Mood Symptoms in Young Adult Cannabis Users.

Objective: The endocannbinoid system and cannabis exposure has been implicated in emotional processing. The current study examined whether regular cannabis users demonstrated abnormal intrinsic (a.k.a. resting state) frontolimbic connectivity compared to non-users. A secondary aim examined the relationship between cannabis group connectivity differences and self-reported mood and affect symptoms. Method: Participants included 79 cannabis-using and 80 non-using control emerging adults (ages of 18-30), balanced for gender, reading ability, and age. Standard multiple regressions were used to predict if cannabis group status was associated with frontolimbic connectivity after controlling for site, past month alcohol and nicotine use, and days of abstinence from cannabis. Results: After controlling for research site, past month alcohol and nicotine use, and days of abstinence from cannabis, cannabis users demonstrated significantly greater connectivity between left rACC and the following: right rACC (p = 0.001; corrected p = 0.05; f 2 = 0.55), left amygdala (p = 0.03; corrected p = 0.47; f 2 = 0.17), and left insula (p = 0.03; corrected p = 0.47; f 2 = 0.16). Among cannabis users, greater bilateral rACC connectivity was significantly associated with greater subthreshold depressive symptoms (p = 0.02). Conclusions: Cannabis using young adults demonstrated greater connectivity within frontolimbic regions compared to controls. In cannabis users, greater bilateral rACC intrinsic connectivity was associated with greater levels of subthreshold depression symptoms. Current findings suggest that regular cannabis use during adolescence is associated with abnormal frontolimbic connectivity, especially in cognitive control and emotion regulation regions

Worth the wait: effects of age of onset of marijuana use on white matter and impulsivity

Rationale: Marijuana (MJ) use continues to rise, and as the perceived risk of using MJ approaches an all-time historic low, initiation of MJ use is occurring at even younger ages. As adolescence is a critical period of neuromaturation, teens and emerging adults are at greater risk for experiencing the negative effects of MJ on the brain. In particular, MJ use has been shown to be associated with alterations in frontal white matter microstructure, which may be related to reports of increased levels of impulsivity in this population. Objectives: The aim of this study was to examine the relationship between age of onset of MJ use, white matter microstructure, and reported impulsivity in chronic, heavy MJ smokers. Methods: Twenty-five MJ smokers and 18 healthy controls underwent diffusion tensor imaging and completed the Barratt Impulsiveness Scale. MJ smokers were also divided into early onset (regular use prior to age 16) and late onset (age 16 or later) groups in order to clarify the impact of age of onset of MJ use on these variables. Results: MJ smokers exhibited significantly reduced fractional anisotropy (FA) relative to controls, as well as higher levels of impulsivity. Earlier MJ onset was also associated with lower levels of FA. Interestingly, within the early onset group, higher impulsivity scores were correlated with lower FA, a relationship that was not observed in the late onset smokers. Conclusions: MJ use is associated with white matter development and reported impulsivity, particularly in early onset smokers

Chemical Reactions: Marijuana, Opioids, and Our Families

Chemical Reactions: Marijuana, Opioids, and Our Families is the seventh Massachusetts Family Impact Seminar. This seminar was designed to emphasize a family perspective in policymaking on issues related to the legalization of marijuana and managing the opioid abuse crisis in the Commonwealth. In general, Family Impact Seminars analyze the consequences an issue, policy, or program may have for families

Joint Effects: A Pilot Investigation of the Impact of Bipolar Disorder and Marijuana Use on Cognitive Function and Mood

Marijuana is the most widely used illicit substance in those diagnosed with bipolar I disorder. However, there is conflicting evidence as to whether marijuana may alleviate or exacerbate mood symptomatology. As bipolar disorder and marijuana use are individually associated with cognitive impairment, it also remains unclear whether there is an additive effect on cognition when bipolar patients use marijuana. The current study aimed to determine the impact of marijuana on mood in bipolar patients and to examine whether marijuana confers an additional negative impact on cognitive function. Twelve patients with bipolar disorder who smoke marijuana (MJBP), 18 bipolar patients who do not smoke (BP), 23 marijuana smokers without other Axis 1 pathology (MJ), and 21 healthy controls (HC) completed a neuropsychological battery. Further, using ecological momentary assessment, participants rated their mood three times daily as well as after each instance of marijuana use over a four-week period. Results revealed that although the MJ, BP, and MJBP groups each exhibited some degree of cognitive impairment relative to HCs, no significant differences between the BP and MJBP groups were apparent, providing no evidence of an additive negative impact of BPD and MJ use on cognition. Additionally, ecological momentary assessment analyses indicated alleviation of mood symptoms in the MJBP group after marijuana use; MJBP participants experienced a substantial decrease in a composite measure of mood symptoms. Findings suggest that for some bipolar patients, marijuana may result in partial alleviation of clinical symptoms. Moreover, this improvement is not at the expense of additional cognitive impairment

Elevated Preattentive Affective Processing in Individuals with Borderline Personality Disorder: A Preliminary fMRI Study

Background: Emotion dysregulation is central to the clinical conceptualization of borderline personality disorder (BPD), with individuals often displaying instability in mood and intense feelings of negative affect. Although existing data suggest important neural and behavioral differences in the emotion processing of individuals with BPD, studies thus far have only explored reactions to overt emotional information. Therefore, it is unclear if BPD-related emotional hypersensitivity extends to stimuli presented below the level of conscious awareness (preattentively). Methods: Functional magnetic resonance imaging (fMRI) was used to measure neural responses to happy, angry, fearful, and neutral faces presented preattentively, using a backward masked affect paradigm. Given their tendency toward emotional hyperreactivity and altered amygdala and frontal activation, we hypothesized that individuals with BPD would demonstrate a distinct pattern of fMRI responses relative to those without BPD during the viewing of masked affective versus neutral faces in specific regions of interests (ROIs). Results: Results indicated that individuals with BPD demonstrated increases in frontal, cingulate, and amygdalar activation represented by number of voxels activated and demonstrated a different pattern of activity within the ROIs relative to those without BPD while viewing masked affective versus neutral faces. Conclusion: These findings suggest that in addition to the previously documented heightened responses to overt displays of emotion, individuals with BPD also demonstrate differential responses to positive and negative emotions, early in the processing stream, even before conscious awareness

Neuroimaging-Based Classification of PTSD Using Data-Driven Computational Approaches:A Multisite Big Data Study from the ENIGMA-PGC PTSD Consortium

BACKGROUND: Recent advances in data-driven computational approaches have been helpful in devising tools to objectively diagnose psychiatric disorders. However, current machine learning studies limited to small homogeneous samples, different methodologies, and different imaging collection protocols, limit the ability to directly compare and generalize their results. Here we aimed to classify individuals with PTSD versus controls and assess the generalizability using a large heterogeneous brain datasets from the ENIGMA-PGC PTSD Working group.METHODS: We analyzed brain MRI data from 3,477 structural-MRI; 2,495 resting state-fMRI; and 1,952 diffusion-MRI. First, we identified the brain features that best distinguish individuals with PTSD from controls using traditional machine learning methods. Second, we assessed the utility of the denoising variational autoencoder (DVAE) and evaluated its classification performance. Third, we assessed the generalizability and reproducibility of both models using leave-one-site-out cross-validation procedure for each modality.RESULTS: We found lower performance in classifying PTSD vs. controls with data from over 20 sites (60% test AUC for s-MRI, 59% for rs-fMRI and 56% for d-MRI), as compared to other studies run on single-site data. The performance increased when classifying PTSD from HC without trauma history in each modality (75% AUC). The classification performance remained intact when applying the DVAE framework, which reduced the number of features. Finally, we found that the DVAE framework achieved better generalization to unseen datasets compared with the traditional machine learning frameworks, albeit performance was slightly above chance.CONCLUSION: These results have the potential to provide a baseline classification performance for PTSD when using large scale neuroimaging datasets. Our findings show that the control group used can heavily affect classification performance. The DVAE framework provided better generalizability for the multi-site data. This may be more significant in clinical practice since the neuroimaging-based diagnostic DVAE classification models are much less site-specific, rendering them more generalizable.</p

Splendor in the Grass? A Pilot Study Assessing the Impact of Medical Marijuana on Executive Function

Currently, 25 states and Washington DC have enacted full medical marijuana (MMJ) programs while 18 states allow limited access to MMJ products. Limited access states permit low (or zero) tetrahydrocannabinol (THC) and high cannabidiol (CBD) products to treat specified conditions such as uncontrolled epilepsy. Although MMJ products are derived from the same plant species as recreational MJ, they are often selected for their unique cannabinoid constituents and ratios, not typically sought by recreational users, which may impact neurocognitive outcomes. To date, few studies have investigated the potential impact of MMJ use on cognitive performance, despite a well-documented association between recreational marijuana (MJ) use and executive dysfunction. The current study assessed the impact of three months of MMJ treatment on executive function, exploring whether MMJ patients would experience improvement in cognitive functioning, perhaps related to primary symptom alleviation. As part of a larger longitudinal study, 24 patients certified for MMJ use completed baseline executive function assessments and 11 of these so far have returned for their first follow-up visit three months after initiating treatment. Results suggest that in general, MMJ patients experienced some improvement on measures of executive functioning, including the Stroop Color Word Test and Trail Making Test, mostly reflected as increased speed in completing tasks without a loss of accuracy. On self-report questionnaires, patients also indicated moderate improvements in clinical state, including reduced sleep disturbance, decreased symptoms of depression, attenuated impulsivity, and positive changes in some aspects of quality of life. Additionally, patients reported a notable decrease in their use of conventional pharmaceutical agents from baseline, with opiate use declining more than 42%. While intriguing, these findings are preliminary and warrant further investigation at additional time points and in larger sample sizes. Given the likelihood of increased MMJ use across the country, it is imperative to determine the potential impact of short- and long-term treatment on cognitive performance as well as the efficacy of MMJ treatment itself