8:30 am Coffee and Morning Networking
9:00 am Chair’s Opening Remarks
Striving for Useful Biomarkers in Clinical Practice
9:10 am Panel Discussion: Exploring Novel Electrophysiological Biomarkers of Synaptic Plasticity in Humans
Synopsis
• To explore what are the most promising electrophysiological biomarkers to probe plasticity in the human brain
• Understand how sensitive synaptic plasticity biomarkers are in detecting disease related impairments in plasticity (regional or network)
• Understand the pharmacological sensitivity of novel synaptic plasticity biomarkers
10:10 am Thalamo-cortical Dysconnectivity in Schizophrenia & Youth a High Clinical Risk for Schizophrenia
Synopsis
• Compared to people unaffected with schizophrenia, people with schizophrenia (SZ) have less connectivity between the thalamus and both frontal lobe areas and cerebellum
• SZ have more hyperconnectivity between thalamus and temporal lobe
• Hypo-connectivity to cerebellum in SZ is related to delusions and bizarre behavior
• Hyper-connectivity to auditory cortex in SZ is related to hallucination and delusion severity
• Youth at clinical high risk for psychosis show a similar pattern of hypoand hyper-thalamo-cortical connectivity
10:35 am A neural circuits platform to accelerate and de-risk preclinical neuropsychiatric drug development
Synopsis
• The need for improved in-vivo, in-brain pharmacodynamic readouts for
preclinical therapeutic development
• The Inscopix neural circuits platform for circuit-based
pharmacodynamics and efficacy assessments
• Case study: striatal circuit signatures corresponding to optimal
antipsychotic effect and clinical performance
10:50 am Live Q&A
11:05 am Networking Break
11:35 am Investigating Sensory ERP Biomarkers for Disease & Target Engagement
Synopsis
• Leveraging neurophysiological methods to investigate the role of NMDA receptors in sensory processes such as auditory mismatch negativity (MMN) and visual magnocellular activity
• Mismatch negativity as a tool for translational investigations
• What new insights do we have in contributions of sensory dysfunction to impairments in higher level processes in schizophrenia?
• Excitation / Inhibition Targeted Drug Therapy
12:00 pm Implementation of a Multi-Modal Brain Stimulation Approach in Early Stage Clinical Trials
Synopsis
• Transcranial Magnetic Stimulation (TMS) electrodiagnostic markers in Phase 1a studies to investigate pharmacodynamic profiles of novel drugs;
• Development of TMS electrodiagnostic markers as a tool to assess human brain excitability in neurological conditions
• Can we develop TMS-electrodiagnostic markers as a test to track disease progression and to evaluate the beneficial effects of pharmacological treatments?
12:25 pm Precision Medicine in Psychiatric Drug Development
Synopsis
• Important challenges for novel drug development include patient heterogeneity and lack of established biomarkers to help with patient selection
• Genetic information may help, but it will not be enough. The field needs to seek and validate multimodal biomarker approaches
• Biomarkers that capture functional state of relevant neural circuits will be important to test. A significant amount of investigation is taking place in this area.
• We need to think of patient subsets that are ideal for the mechanism of action of novel treatments, and this should rely on domain-related multimodal biomarkers as well as disease staging.
12:50 pm Live Q&A
1:05 pm Lunch Break and Networking
Exploring the Emerging Possibilities that Digital Therapeutics Offer Neuropsychiatric Patients
2:05 pm Panel Discussion: How Best Can We Drive a Patient Centric Approach to Develop Efficacious & Engaging Digital Therapeutics?
Synopsis
• How can we establish digital therapeutics as a meaningful new treatment category for patients?
• How can these new digital therapeutics complement novel treatments being developed specifically for neuropsychiatric diseases?
• What is the best approach to develop these digital therapeutics?
• How can we regulate them? Do you want to combine, pair your drug product with a specific digital therapy?
• How should we program it right and make it user friendly?
• Would a company commission their own digital therapeutic to pair with another companies’ new product?
3:05 pm Neuropsychiatric Implications of COVID 19
Synopsis
• Assess the psychiatric and neuropsychiatric presentations of COVID-19
and investigate the COVID-19-psychosis relationship
• The associations between psychosis and COVID-19 cited in the literature
will be reviewed and potential mechanisms will be discussed
• Delirium in COVID-19 is common and serious. Causal mechanisms for
neuropsychiatric sequelae are likely to include systemic inflammation
and psychosocial factors. There is likely to be long-term neuropsychiatric
morbidity due to stroke, psychiatric disease and long-COVID
3:35 pm Coffee and networking break
How Pivotal is Neuroinflammation Across Neuropsychaitric Disorders?
4:05 pm Inflammatory Mechanisms of Cognitive Dysfunction in Bipolar Disorder
Synopsis
• Describe the neurocognitive profile seen in bipolar disorder
• Identify peripheral immune markers of cognitive dysfunction and heterogeneity in bipolar disorder
• Discussion application of available neuroimaging strategies for in-vivo characterization of CNS immune activation
4:30 pm Dysregulated NeuroImmune Axes in Mood Disorders
Synopsis
• Role of microglia, neuroinflammation and peripheral immune cells in mood disorders
• Discovery and development of brain penetrant P2X7 antagonists, a microglial target (P2X7-NLRP3 pathway)
• What neuroinflammatory PET imaging agents are being developed that would be useful?
• Other neuroinflammatory biomarkers
4:55 pm TNF Inhibition as Treatment for Treatment-Resistant Depression
Synopsis
• The role of neuroinflammation in treatment resistant depression: review of the evidence
• Development of a Phase 2 study of the soluble TNF inhibitor Xpro1595 in treatment resistant depression
• Use of noninvasive biomarkers for patient selection, target engagement and treatment response
5:20 pm Pharmacotranscriptomic Profiling & Molecular Mechanisms Triggered by Antipsychotics: Boosting the Search of New Drug Targets in Schizophrenia
Synopsis
• Brief overview of state-of-the-art knowledge of how
pharmacotranscriptomics serves as a valuable method to permit target
discovery and evaluate drug efficacy.
• How antipsychotics may modulate expression of inflammatory cytokines
and inducible inflammatory enzymes.
• A better understanding of the molecular mechanisms that participate in
clinical manifestations of schizophrenia and treat this disease.