Core Readings

Week 1: Epilepsy

Current landscape of epilepsy genetics (Ruggiero & Helbig, 2023)

Key Points:

  • Genetic testing for all individuals with an unexplained epilepsy is now standard-of-care, with exome sequencing often being the most appropriate test of choice.

  • Increased genetic testing of individuals & huge multinational exome sequencing and datasharing efforts have led to further genotypic and phenotypic characterization in the epilepsies.

  • Collaboration with disease advocacy organizations has pushed the field of epilepsy genetics and precision medicine forward.

Pace of gene discovery is continuing at a steady pace but slowing over time as we reach the limits of gene discovery power achievable with current exome studies.

Knowledge of phenotypic characterization continues to rapidly increase, leveraged by large studies of many hundreds of individuals with genetic epilepsy.

Evidence supporting the validity of gene-disease relationship is bolstered over time by repeated case series, natural history analyses and evidence gained from functional testing.

  • Mounting genetic and experimental evidence also leads to gene-disease relationships being refuted over time.

Development of 1st gene modulatory therapies in genetic epilepsies

Jia et al., 2020 — Reconfiguration of dynamic brain network f. connectivity in generalized tonic-clonic seizures (GTCS)

Patients with GTCS demonstrate reliable abnormality of FC temporal variability in cognition related function networks, suggesting frequent information communication among them that may implicate epileptic activity & cognitive deficits.

  • Significant increases in variability particularly involving the default mode network (DMN)

Increased FC temporal variability in motor-related regions might be associated with motor dysfunction in GTCS.

:. GTCS is associated with reconfiguration of brain network dynamics, particularly involving heightened temporal variability in DMN connectivity.

  • Temporal variability of FC = sensitive marker of brain network reorganization in GTCS.

  • Abnormal DMN dynamics may play a central role in the pathophysiology of GTCS.

Suzuki, K. & M., 2022 — Optical analysis of AMPAR-mediated synaptic scaling in mouse hippocampus.

Immunolabeling of surface AMPA receptors (AMPARs) can be used for in vivo or ex vivo examination of synaptic scaling, a type of homeostatic plasticity.

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Week 2: Schizophrenia

Psychosis related to high risk of relapse — 67% clients relapsing within a year following 1st episodes

Individuals with psychosis demonstrate high levels of psychosocial stress and are more likely to be socially withdrawn.

There is significant association between psychosocial stress and psychosis relapse, as well as between social withdrawal and psychosis relapse.

Individuals with psychosis tend to experience high levels of psychosocial stress and social withdrawal, and these appear to increase the risk of psychosis relapse.