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It is not clear to what extent associations between schizophrenia, cannabis use and cigarette use are due to a shared genetic etiology. We, therefore, examined whether schizophrenia genetic risk associates with longitudinal patterns of cigarette and cannabis use in adolescence and mediating pathways for any association to inform potential reduction strategies.
Associations between schizophrenia polygenic scores and longitudinal latent classes of cigarette and cannabis use from ages 14 to 19 years were investigated in up to 3925 individuals in the Avon Longitudinal Study of Parents and Children. Mediation models were estimated to assess the potential mediating effects of a range of cognitive, emotional, and behavioral phenotypes.
The schizophrenia polygenic score, based on single nucleotide polymorphisms meeting a training-set p threshold of 0.05, was associated with late-onset cannabis use (OR = 1.23; 95% CI = 1.08,1.41), but not with cigarette or early-onset cannabis use classes. This association was not mediated through lower IQ, victimization, emotional difficulties, antisocial behavior, impulsivity, or poorer social relationships during childhood. Sensitivity analyses adjusting for genetic liability to cannabis or cigarette use, using polygenic scores excluding the CHRNA5-A3-B4 gene cluster, or basing scores on a 0.5 training-set p threshold, provided results consistent with our main analyses.
Our study provides evidence that genetic risk for schizophrenia is associated with patterns of cannabis use during adolescence. Investigation of pathways other than the cognitive, emotional, and behavioral phenotypes examined here is required to identify modifiable targets to reduce the public health burden of cannabis use in the population.
Pathological worry is a hallmark feature of generalised anxiety disorder (GAD), associated with dysfunctional emotional processing. The ventromedial prefrontal cortex (vmPFC) is involved in the regulation of such processes, but the link between vmPFC emotional responses and pathological v. adaptive worry has not yet been examined.
To study the association between worry and vmPFC activity evoked by the processing of learned safety and threat signals.
In total, 27 unmedicated patients with GAD and 56 healthy controls (HC) underwent a differential fear conditioning paradigm during functional magnetic resonance imaging.
Compared to HC, the GAD group demonstrated reduced vmPFC activation to safety signals and no safety–threat processing differentiation. This response was positively correlated with worry severity in GAD, whereas the same variables showed a negative and weak correlation in HC.
Poor vmPFC safety–threat differentiation might characterise GAD, and its distinctive association with GAD worries suggests a neural-based qualitative difference between healthy and pathological worries.
Current guidelines recommend that patients with CHD receive age-appropriate counselling on reproduction, pregnancy, and risk of heredity. Our aim was to examine patient knowledge of reproductive health and explore the association between patient knowledge of CHD transmission risk and earlier physician counselling in adults with CHD.
We performed a cross-sectional survey of patients with CHD aged 18 years and older in a paediatric hospital.
Of the 100 patients who completed the questionnaire, most did not report counselling on heredity (66%) or contraception (71%). Of the 54 women, 25 (46%) identified their contraceptive options correctly; 42 (78%) women were classified as being at significantly increased risk for an adverse outcome during pregnancy, and of these 20 (48%) identified this risk correctly. Of all patients surveyed, 72% did not know that having CHD placed them at increased risk for having a child with CHD. On multivariate analysis, factors associated with correct knowledge about risk of recurrence were correct identification of CHD diagnosis (p=0.04) and patient-reported counselling (p=0.001).
Knowledge about heredity, pregnancy risk, and contraceptive options is inadequate among adults with CHD followed-up in a paediatric subspecialty clinic. The majority of patients did not report a history of counselling about reproductive health. There is a strong correlation between history of counselling by the patient’s cardiologist and correct knowledge about recurrence risk, suggesting that effective reproductive counselling can positively impact this knowledge gap.