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Fear conditioning is an established model for investigating posttraumatic stress disorder (PTSD). However, symptom triggers may vaguely resemble the initial traumatic event, differing on a variety of sensory and affective dimensions. We extended the fear-conditioning model to assess generalization of conditioned fear on fear processing neurocircuitry in PTSD. Military veterans (n=67) consisting of PTSD (n=32) and trauma-exposed comparison (n=35) groups underwent functional magnetic resonance imaging during fear conditioning to a low fear-expressing face while a neutral face was explicitly unreinforced. Stimuli that varied along a neutral-to-fearful continuum were presented before conditioning to assess baseline responses, and after conditioning to assess experience-dependent changes in neural activity. Compared with trauma-exposed controls, PTSD patients exhibited greater post-study memory distortion of the fear-conditioned stimulus toward the stimulus expressing the highest fear intensity. PTSD patients exhibited biased neural activation toward high-intensity stimuli in fusiform gyrus (P<0.02), insula (P<0.001), primary visual cortex (P<0.05), locus coeruleus (P<0.04), thalamus (P<0.01), and at the trend level in inferior frontal gyrus (P=0.07). All regions except fusiform were moderated by childhood trauma. Amygdala–calcarine (P=0.01) and amygdala–thalamus (P=0.06) functional connectivity selectively increased in PTSD patients for high-intensity stimuli after conditioning. In contrast, amygdala–ventromedial prefrontal cortex (P=0.04) connectivity selectively increased in trauma-exposed controls compared with PTSD patients for low-intensity stimuli after conditioning, representing safety learning. In summary, fear generalization in PTSD is biased toward stimuli with higher emotional intensity than the original conditioned-fear stimulus. Functional brain differences provide a putative neurobiological model for fear generalization whereby PTSD symptoms are triggered by threat cues that merely resemble the index trauma.

Background and Aims Studies have consistently found a longitudinal association between e‐cigarette use (vaping) and cigarette smoking. Many have interpreted such association as causal. This systematic review and meta‐analysis evaluated the plausibility of a causal interpretation by (1) estimating the effect of adolescent vaping on smoking initiation, adjusted for study quality characteristics, (2) evaluating the sufficiency of adjustment for confounding based on the social development model (SDM) and the social ecological model (SEM) and E‐value analyses and (3) investigating sample attrition and publication bias. Methods Systematic review and meta‐analysis of longitudinal studies that examined the association between e‐cigarette use at baseline and smoking at follow‐up. Participants were non‐smokers aged < 18 at baseline. Results Meta‐analysis of 11 studies showed a significant longitudinal association between vaping and smoking [adjusted odds ratio (aOR) = 2.93, 95% confidence interval (CI) = 2.22, 3.87]. Studies with sample sizes < 1000 had a significantly higher odds ratio (OR = 6.68, 95% CI = 3.63, 12.31) than studies with sample sizes > 1000 (OR = 2.49, 95% CI = 1.97, 3.15). Overall, the attrition rate was very high (median = 30%). All but one study reported results from complete sample analysis, despite those dropping out having higher risk profiles. Only two studies comprehensively adjusted for confounding. The median E‐value was 2.90, indicating that the estimates were not robust against unmeasured confounding. Conclusions There is a longitudinal association between adolescent vaping and smoking initiation; however, the evidence is limited by publication bias, high sample attrition and inadequate adjustment for potential confounders.

Rationale There has been increasing attention on cannabis use for medical purposes, but there is currently a lack of data on its epidemiology. Objectives To examine the epidemiology of self-reported cannabis use for medical purposes by (1) estimating its prevalence, (2) comparing gender and age differences, and (3) investigating what reasons they were used to manage. Methods Participants included 27,169 respondents (aged 16–65) who completed Wave 1 of The International Cannabis Policy Study (ICPS) conducted across Canada and the USA in 2018 via online surveys. Cannabis policy conditions were “US legal–recreational” (legal for both recreational and medical uses), “US legal–medical only”, “US illegal”, and “Canada–medical only”. Results The overall prevalence of self-reported ever cannabis use for medical purposes was 27%, with similar rates by sex and the highest prevalence in young adults. Prevalence was higher in US legal–recreational states (34%) than US illegal states (23%), US legal–medical only states (25%), and Canada (25%). The most common physical health reasons include use to manage pain (53%), sleep (46%), headaches/migraines (35%), appetite (22%), and nausea/vomiting (21%). For mental health reasons, the most common were for anxiety (52%), depression (40%), and PTSD/trauma (17%). There were 11% who reported using cannabis for managing other drug or alcohol use and 4% for psychosis. Conclusions A substantial proportion of the North American population self-reported cannabis use for medical purposes for a variety of medical reasons, including those living in jurisdictions without legal markets. Further research is needed to understand the safety and efficacy of these forms of medical cannabis use.