PL-02 | Interpersonal psychotherapy – A global reach
Psychotherapy has undergone major developments in standardization, manual descriptions and testing of efficacy in clinical trials . This talk will describe Interpersonal Psychotherapy its content, efficacy and implementation all over the world .
Much epidemiological evidence demonstrates that cannabis use is associated with increased risk of subsequent onset of psychosis. Our work shows a) a dose-response relationship between the level of use and the risk of later psychosis; b) that continued use by those with established psychosis is associated with a worse outcome, and c) experimental administration of tetrahydrocannabinol (THC), the active ingredient of cannabis, induces transient psychosis in normal subjects; this effect may be ameliorated by co-administration of cannabidiol CBD which is present in traditional but not in most modern high potency types of cannabis. Our Trans-European study of 16 sites demonstrates that daily use of high potency cannabis has a significant impact on the incidence of psychosis. The greatest effects were in the cities where high potency cannabis was most available, Amsterdam and London, where 50% and 32% respectively of first episode cases of psychosis could be attributed to daily use of high potency cannabis. Evidence that increased use of cannabis is associated with an increase in new cases psychosis of psychosis comes from Portugal, UK and Canada. Genetic predisposition to schizophrenia has at most a very small effect on cannabis use; polygenic risk for schizophrenia and cannabis use have independent effects on risk rather than correlation or interaction. The evidence that regular use of high potency cannabis is a component cause of psychosis is now sufficient for public health messages outlining the risk.
PL-04 | Stem cells in mental disorders: new understanding and treatment
The complex genetic mechanisms underlying psychiatric and neurodegenerative disease remain unclear. We employ a functional genomics approach that integrates stem cell models and genome engineering, resolving the combinatorial impact of patient-specific variants across cell types, donor genetic backgrounds, and environmental contexts. Individually small risk effects combine to yield much larger impacts in aggregate, but the interactions between the myriad variants remain undetermined. First, we evaluated the impact of patient-specific NRXN1+/- deletions in hiPSC-neurons, observing greater than two-fold reduction of half of the wildtype NRXN1α isoforms and detecting dozens of novel isoforms expressed from the mutant allele; reduced neuronal activity in patient hiPSC-neurons was ameliorated by overexpression of individual control isoforms in a genotype-dependent manner, whereas individual mutant isoforms decreased neuronal activity levels in control hiPSC-neurons. Second, we integrated CRISPR-mediated gene editing, activation and repression technologies to study putative causal common variants and their associated target genes, alone and in combination. This allowed us to uncover an unexpected synergistic effect between risk genes that converges on synaptic function and links the rare and common variant genes implicated in psychiatric disease risk, one which may represent a generalizable phenomenon occurring more widely in complex genetic disorders. We demonstrate a systematic and scalable strategy to interpret and evaluate the additive impact of a growing number of disease-associated variants and genes within and across pathways, neural cell types and treatments. We seek to decode highly complex genetic insights into medically actionable information, better connecting the expanding list of genetic loci associated with human disease to pathophysiology. Our goal is to improve diagnostics, predict clinical trajectories, and identify pre-symptomatic points of therapeutic intervention.