Types of cannabis and tobacco/nicotine co-use and associated outcomes in young adulthood
Tucker JS, Pedersen ER, Seelam R, Dunbar MS, Shih RA, D’Amico EJ. Types of cannabis and tobacco/nicotine co-use and associated outcomes in young adulthood. Psychology of Addictive Behaviors. 2019. https://doi.org/10.1037/adb0000464
Cannabis and tobacco/nicotine use are highly comorbid. Given expanding access to cannabis through legalization for recreational use, it is important to understand how patterns of cannabis and tobacco/nicotine co-use are associated with young adult outcomes. A predominantly California-based sample of 2,429 young adults (mean age = 20.7) completed an online survey. Based on past-year reports of cannabis and tobacco/nicotine use, we defined 5 mutually exclusive groups: (a) single-product use; (b) concurrent use only (using both products, but only on separate occasions); (c) sequential use only (using both products on the same occasion, one right after the other, but not mixing them together); (d) coadministration only (using both products on the same occasion by mixing them in the same delivery device); and (e) both sequential use and coadministration. We examined group differences in use patterns, dependence, consequences of use, and psychosocial functioning. Fifty percent of respondents reported cannabis use, 43% tobacco/nicotine use, and 37% co-use of both substances. The most prevalent method of co-use involved smoking combustible products. Overall, individuals who co-used both substances on the same occasion in some way reported heavier use and greater problematic behaviors than those who did not. Sequential use (especially among those that also engaged in coadministration) was typically associated with worse physical and mental functioning overall compared to using each substance separately. Findings illuminate both prevalence and risks associated with co-use of cannabis and tobacco/nicotine products and can inform policies for states considering regulation of cannabis and tobacco/nicotine products.
Decreased Nociceptin Receptors Are Related to Resilience and Recovery in College Women Who Have Experienced Sexual Violence: Therapeutic Implications for Posttraumatic Stress Disorder
Narendran R, Tollefson S, Fasenmyer K, et al. Decreased nociceptin receptors are related to resilience and recovery in college women who have experienced sexual violence: Therapeutic implications for posttraumatic stress disorder. Biological Psychiatry. 2019. https://doi.org/10.1016/j.biopsych.2019.02.017.
Posttraumatic stress disorder (PTSD) is a stress disorder that develops in only some individuals following a traumatic event. Data suggest that a substantial fraction of women recover after sexual violence. Thus, the investigation of stress and antistress neuropeptides in this sample has the potential to inform the neurochemistry of resilience following trauma. Nociceptin is an antistress neuropeptide in the brain that promotes resilience in animal models of PTSD.
[11C]NOP-1A positron emission tomography was used to measure the in vivobinding to nociceptin receptors in 18 college women who had experienced sexual violence irrespective of whether they met DSM-5 diagnostic criteria for PTSD. [11C]NOP-1A data from 18 healthy control subjects were also included to provide a contrast with the sexual violence group. [11C]NOP-1A total distribution volume (VT) in the regions of interest were measured with kinetic analysis using the arterial input function. The relationships between regional VT and Clinician-Administered PTSD Scale for DSM-5 total symptom and subscale severity were examined using correlational analyses.
No differences in [11C]NOP-1A VT were noted between the sexual violence and control groups. VT in the midbrain and cerebellum were positively correlated with PTSD total symptom severity in the past month before positron emission tomography. Intrusion/re-experiencing and avoidance subscale symptoms drove this relationship. Stratification of subjects by a DSM-5 PTSD diagnosis and contrasting their VT with that in control subjects showed no group differences.
Decreased midbrain and cerebellum nociceptin receptors are associated with less severe PTSD symptoms. Medications that target nociceptin should be explored to prevent and treat PTSD.
Towards Artificial Intelligence in Mental Health by Improving Schizophrenia Prediction with Multiple Brain Parcellation Ensemble-Learning
Kalmady SV, Greiner R, Agrawal R, et al. Towards artificial intelligence in mental health by improving schizophrenia prediction with multiple brain parcellation ensemble-learning. npj Schizophrenia. 2019;5(1):2. https://doi.org/10.1038/s41537-018-0070-8.
In the literature, there are substantial machine learning attempts to classify schizophrenia based on alterations in resting-state (RS) brain patterns using functional magnetic resonance imaging (fMRI). Most earlier studies modelled patients undergoing treatment, entailing confounding with drug effects on brain activity, and making them less applicable to real-world diagnosis at the point of first medical contact. Further, most studies with classification accuracies >80% are based on small sample datasets, which may be insufficient to capture the heterogeneity of schizophrenia, limiting generalization to unseen cases. In this study, we used RS fMRI data collected from a cohort of antipsychotic drug treatment-naive patients meeting DSM IV criteria for schizophrenia (N = 81) as well as age- and sex-matched healthy controls (N = 93). We present an ensemble model — EMPaSchiz (read as ‘Emphasis’; standing for ‘Ensemble algorithm with Multiple Parcellations for Schizophrenia prediction’) that stacks predictions from several ‘single-source’ models, each based on features of regional activity and functional connectivity, over a range of different a priori parcellation schemes. EMPaSchiz yielded a classification accuracy of 87% (vs. chance accuracy of 53%), which out-performs earlier machine learning models built for diagnosing schizophrenia using RS fMRI measures modelled on large samples (N > 100). To our knowledge, EMPaSchiz is first to be reported that has been trained and validated exclusively on data from drug-naive patients diagnosed with schizophrenia. The method relies on a single modality of MRI acquisition and can be readily scaled-up without needing to rebuild parcellation maps from incoming training images.
Identification of common genetic risk variants for autism spectrum disorder
Grove J, Ripke S, Als TD, et al. Identification of common genetic risk variants for autism spectrum disorder. Nat Genet. 2019;51(3):431-444. https://doi.org/10.1038/s41588-019-0344-8.
Autism spectrum disorder (ASD) is a highly heritable and heterogeneous group of neurodevelopmental phenotypes diagnosed in more than 1% of children. Common genetic variants contribute substantially to ASD susceptibility, but to date no individual variants have been robustly associated with ASD. With a marked sample-size increase from a unique Danish population resource, we report a genome-wide association meta-analysis of 18,381 individuals with ASD and 27,969 controls that identified five genome-wide-significant loci. Leveraging GWAS results from three phenotypes with significantly overlapping genetic architectures (schizophrenia, major depression, and educational attainment), we identified seven additional loci shared with other traits at equally strict significance levels. Dissecting the polygenic architecture, we found both quantitative and qualitative polygenic heterogeneity across ASD subtypes. These results highlight biological insights, particularly relating to neuronal function and corticogenesis, and establish that GWAS performed at scale will be much more productive in the near term in ASD.
Acceptability and Preliminary Efficacy of an Online HIV Prevention Intervention for Single Young Men Who Have Sex with Men Seeking Partners Online: The myDEx Project
Bauermeister JA, Tingler RC, Demers M, et al. Acceptability and preliminary efficacy of an online HIV prevention intervention for single young men who have sex with men seeking partners online: The myDEx project. AIDS and Behavior. 2019. https://doi.org/10.1007/s10461-019-02426-7.
Prevention of new cases of HIV among young gay, bisexual and other men who have sex with men (YGBMSM; ages 18–24) remains a priority. We developed and pilot tested an online intervention (myDEx) using a pilot randomized trial design with 180 online-recruited single YGBMSM who reported recent unprotected anal intercourse, self-reporting as HIV negative or status-unaware, and who met sexual partners through online dating applications. myDEx participants reported higher overall satisfaction (d = 0.46) and willingness to recommend the intervention to friends (d = 0.48) than controls. myDEx participants were less likely to report foregoing condoms to achieve an emotional connection with a partner (d =0 .43), and more likely to report greater emotional regulation during their partner-seeking behaviors (d = 0.44). myDEx participants reported fewer partners with whom they had condomless receptive anal sex (d = 0.48). Our pilot results demonstrate the potential of the myDEx intervention, suggesting that a larger efficacy trial may be warranted in the future.
Enhanced recovery after elective spinal and peripheral nerve surgery: pilot study from a single institution
Ali ZS, Flanders TM, Ozturk AK, et al. Enhanced recovery after elective spinal and peripheral nerve surgery: Pilot study from a single institution. Journal of Neurosurgery: Spine SPI. 2019:1-9. https://dx.doi.org/10.3171/2018.9.SPINE18681.
Enhanced recovery after surgery (ERAS) protocols address pre-, peri-, and postoperative factors of a patient’s surgical journey. The authors sought to assess the effects of a novel ERAS protocol on clinical outcomes for patients undergoing elective spine or peripheral nerve surgery.
The authors conducted a prospective cohort analysis comparing clinical outcomes of patients undergoing elective spine or peripheral nerve surgery after implementation of the ERAS protocol compared to a historical control cohort in a tertiary care academic medical center. Patients in the historical cohort (September–December 2016) underwent traditional surgical care. Patients in the intervention group (April–June 2017) were enrolled in a unique ERAS protocol created by the Department of Neurosurgery at the University of Pennsylvania. Primary objectives were as follows: opioid and nonopioid pain medication consumption, need for opioid use at 1 month postoperatively, and patient-reported pain scores. Secondary objectives were as follows: mobilization and ambulation status, Foley catheter use, need for straight catheterization, length of stay, need for ICU admission, discharge status, and readmission within 30 days.
A total of 201 patients underwent surgical care via an ERAS protocol and were compared to a total of 74 patients undergoing traditional perioperative care (control group). The 2 groups were similar in baseline demographics. Intravenous opioid medications postoperatively via patient-controlled analgesia was nearly eliminated in the ERAS group (0.5% vs 54.1%, p < 0.001). This change was not associated with an increase in the average or daily pain scores in the ERAS group. At 1 month following surgery, a smaller proportion of patients in the ERAS group were using opioids (38.8% vs 52.7%, p = 0.041). The ERAS group demonstrated greater mobilization on postoperative day 0 (53.4% vs 17.1%, p < 0.001) and postoperative day 1 (84.1% vs 45.7%, p < 0.001) compared to the control group. Postoperative Foley use was decreased in the ERAS group (20.4% vs 47.3%, p < 0.001) without an increase in the rate of straight catheterization (8.1% vs 11.9%, p = 0.51).
Implementation of this novel ERAS pathway safely reduces patients’ postoperative opioid requirements during hospitalization and 1 month postoperatively. ERAS results in improved postoperative mobilization and ambulation.
Reward behaviour is regulated by the strength of hippocampus–nucleus accumbens synapses
LeGates TA, Kvarta MD, Tooley JR, et al. Reward behaviour is regulated by the strength of hippocampus–nucleus accumbens synapses. Nature. 2018. https://doi.org/10.1038/s41586-018-0740-8.
Reward drives motivated behaviours and is essential for survival, and therefore there is strong evolutionary pressure to retain contextual information about rewarding stimuli. This drive may be abnormally strong, such as in addiction, or weak, such as in depression, in which anhedonia (loss of pleasure in response to rewarding stimuli) is a prominent symptom. Hippocampal input to the shell of the nucleus accumbens (NAc) is important for driving NAc activity1,2 and activity-dependent modulation of the strength of this input may contribute to the proper regulation of goal-directed behaviours. However, there have been few robust descriptions of the mechanisms that underlie the induction or expression of long-term potentiation (LTP) at these synapses, and there is, to our knowledge, no evidence about whether such plasticity contributes to reward-related behaviour. Here we show that high-frequency activity induces LTP at hippocampus–NAc synapses in mice via canonical, but dopamine-independent, mechanisms. The induction of LTP at this synapse in vivo drives conditioned place preference, and activity at this synapse is required for conditioned place preference in response to a natural reward. Conversely, chronic stress, which induces anhedonia, decreases the strength of this synapse and impairs LTP, whereas antidepressant treatment is accompanied by a reversal of these stress-induced changes. We conclude that hippocampus–NAc synapses show activity-dependent plasticity and suggest that their strength may be critical for contextual reward behaviour.
Patients’ Experience With Opioid Tapering: A Conceptual Model With Recommendations for Clinicians
Ahn S, Prim JH, Alexander ML, McCulloch KL, Fröhlich F. Identifying and engaging neuronal oscillations by transcranial alternating current stimulation in patients with chronic low back pain: A randomized, crossover, double-blind, sham-controlled pilot study. The Journal of Pain. . https://doi.org/10.1016/j.jpain.2018.09.004
Clinical guidelines discourage prescribing opioids for chronic pain, but give minimal advice about how to discuss opioid tapering with patients. We conducted focus groups and interviews involving 21 adults with chronic back or neck pain in different stages of opioid tapering. Transcripts were qualitatively analyzed to characterize patients’ tapering experiences, build a conceptual model of these experiences, and identify strategies for promoting productive discussions of opioid tapering. Analyses revealed 3 major themes. First, owing to dynamic changes in patients’ social relationships, emotional state, and health status, patients’ pain and their perceived need for opioids fluctuate daily; this finding may conflict with recommendations to taper by a certain amount each month. Second, tapering requires substantial patient effort across multiple domains of patients’ everyday lives; patients discuss this effort superficially, if at all, with clinicians. Third, patients use a variety of strategies to manage the tapering process (eg, keeping an opioid stash, timing opioid consumption based on planned activities). Recommendations for promoting productive tapering discussions include understanding the social and emotional dynamics likely to impact patients’ tapering, addressing patient fears, focusing on patients’ best interests, providing anticipatory guidance about tapering, and developing an individualized tapering plan that can be adjusted based on patient response.
Perspective: This study used interview and focus group data to characterize patients’ experiences with opioid tapering and identify communication strategies that are likely to foster productive, patient-centered discussions of opioid tapering. Findings will inform further research on tapering and help primary care clinicians to address this important, often challenging topic.
Development and Validation of a Measure to Assess Patients’ Threat Perceptions in the Emergency Department
Cornelius T, Agarwal S, Garcia O, Chaplin W, Edmondson D, Chang BP. Development and validation of a measure to assess patients’ threat perceptions in the emergency department. Acad Emerg Med. 2018;0. https://doi.org/10.1111/acem.13513.
Threat perceptions in the Emergency Department (ED) (e.g., patients’ subjective feelings of helplessness or lack of control) during evaluation for an acute coronary syndrome (ACS) are associated with the development of posttraumatic stress disorder (PTSD), and PTSD has been associated with medication nonadherence, cardiac event recurrence, and mortality. This study reports the development and validation of a 7‐item measure of ED Threat Perceptions in English‐ and Spanish‐speaking patients evaluated for ACS.
Participants were drawn from an observational cohort study of 1,000 patients evaluated for ACS between 2013‐2016 in a large, New York City hospital. Participants reported on threat perceptions in the ED and during inpatient stay (using 12 items previously identified as predictive of PTSD) and reported on cardiac‐induced PTSD one month post‐discharge. Exploratory and confirmatory factor analyses were used to establish the factor structure and test measurement invariance. Validity and reliability were examined, as was the association of ED Threat Perceptions with cardiac‐induced PTSD.
Factor analyses identified a 7‐item measure of ED Threat Perceptions (e.g., “I feel helpless,” “I am worried that I am going to die”) for both English‐ and Spanish‐speaking patients. ED Threat Perceptions demonstrated convergent validity, correlating with ED stress and ED crowdedness (rs = .29, .14), good internal consistency (α = .82), and stability (r = .61). Threat Perceptions were associated with cardiac‐induced acute stress at inpatient and PTSD symptoms at one month (rs = .43, .39).
This brief tool assessing ED Threat Perceptions has clinical utility for providers to identify patients at risk for developing cardiac‐induced PTSD and is critical to inform research on whether threat may be modified in‐ED to reduce PTSD incidence.