Program at a Glance

Details: Thursday, June 9, 15:45 - 16:45 (GMT+8)

Speaker: Prof. Francesco Benedetti, University Vita-Salute San Raffaele, Milano

Chair: Prof. Pierre Blier, University of Ottawa Institute of Mental Health Research, Canada

Description: Immunopsychiatry can be defined as the study of immune-inflammatory pathways in order to identify pathogenetic mechanisms, and targets for treatment in psychiatric conditions. We can affirm that COVID-19 survivors show persistent psychopathology and neurocognitive impairment in around 35% of patients. The cluster of Post-Acute Sequelae of COVID-19 (PASC) symptoms typically emerge after the acute phase of illness, when patients are no longer positive to SARS-CoV-2, including dyspnoea, hypoxia, joint and muscle pain, paraesthesia, dysgeusia, anosmia, fatigue. Unrelated to the latter, there are symptoms of depression, anxiety, insomnia, difficulties in sustained attention and memory, which worsen over the months. Brain correlates involve diffuse disruption of white matter microstructure, reduced grey matter volumes in anterior cingulate cortex, and abnormal functional connectivity in the cortico-limbic circuitries. These are proportional to the degree of persistent systemic inflammation, but not to the severity of the acute illness and the breadth of exposure to stressful events during the pandemic. We suggest that post-COVID depression provides an invaluable model illness for the study of immune-inflammatory mechanisms involved in the pathogenesis of mood disorders to identify new targets to restore mental health and brain homeostasis.

Details: Friday, June 10, 6:15 - 7:15 (GMT+8)

Speaker: Prof. Masashi Yanagisawa, The University of Tsukuba, Japan

Chair: Prof. Noriko Osumi, Tohoku University, Japan

Description: Although sleep is a ubiquitous behavior in animal species with central nervous systems, the neurobiology of sleep remain mysterious. Our discovery of orexin, a hypothalamic neuropeptide involved in the maintenance of wakefulness, has helped reveal neural pathways in the regulation of sleep/wakefulness. Orexin receptor antagonists, which specifically block the endogenous waking system, have been approved as a new drug to treat insomnia. Also, since the sleep disorder narcolepsy-cataplexy is caused by orexin deficiency, orexin receptor agonists are expected to provide mechanistic therapy for narcolepsy; they will likely be also useful for treating excessive sleepiness due to other etiologies. Despite the fact that the executive neurocircuitry and neurochemistry for sleep/wake switching has been increasingly revealed in recent years, the mechanism for homeostatic regulation of sleep, as well as the neural substrate for "sleepiness" (sleep need), remains unknown. To crack open this black box, we have initiated a large-scale forward genetic screen of sleep/wake phenotype in mice based on true somnographic (EEG/EMG) measurements. We have so far screened >10,000 heterozygous ENU-mutagenized founders and established a number of pedigrees exhibiting heritable and specific sleep/wake abnormalities. By combining linkage analysis and the next-generation whole exome sequencing, we have molecularly identified and verified the causal mutations in several of these pedigrees. Biochemical and neurophysiological analyses of these mutations are underway. Indeed, through a systematic cross-comparison of the Sleepy mutants (with a gain-of-function change in a serine/threonine kinase pathway) and sleep-deprived mice, we have found that the cumulative phosphorylation state of a specific set of mostly synaptic proteins may be the molecular substrate of sleep need.

Details: Friday, June 10, 15:15 - 16:15 (GMT+8)

Speakers:

Details: Saturday, June 11, 14:30 - 15:30 (GMT+8)

Speaker: Dr. Hailan Hu, Zhejiang University, China

Chair: Prof. Gabriella Gobbi, McGill University, Montreal, Canada

Description: Ketamine, the N-methyl-D-aspartate receptor (NMDAR) antagonist, has revolutionized depression treatment because of its robust, rapid and sustained antidepressant effects. Recently, it was discovered that ketamine inhibits the NMDAR-dependent burst firing of the brain’s anti-reward center, the lateral habenula (LHb). By silencing the LHb bursts, ketamine can disinhibit the aminergic reward circuits downstream of LHb to exert its rapid antidepressant effects.

However, at least three key questions have remained unaddressed. Firstly, does blockade of LHb burst firing contribute to ketamine’s sustained antidepressant effects? Despite of its rapid metabolic half-life (3 h in human and 13 min in mice), the antidepressant effects of a single application of ketamine can last for 3～14 d in humans and for at least 24 h in mouse models of depression. It will be clinically important to understand to what extent ketamine’s local action in the LHb contributes to its sustained effects. Secondly, given that NMDARs are ubiquitously expressed, which specific brain region is the direct target of ketamine? It will be important to distinguish the primary versus the secondary targets. Thirdly, will a drug targeting the same cellular/circuit mechanism of ketamine have similar antidepressant effects? More specifically, since LHb burst firing requires the synergistic action of both NMDARs and the T-type calcium channel (T-VSCC), can T-VSCC inhibitors be antidepressant?

In this talk, I will present our ongoing efforts in addressing these three urgent questions, which will hopefully illuminate a unified theory on ketamine’s mode of action and inspire new treatment strategies for depression.

Details: Saturday, June 11, 19:45 - 20:45 (GMT+8)

Speaker: Dr. Edward Bullmore, University of Cambridge, United Kingdom

Chair: Dr. John Krystal, Yale School of Medicine, USA

Description: Inflammation is robustly associated with depression and other mental health disorders. However, there are many open questions about the causal relationships that might explain the increasing mass of largely correlational findings. I will review several approaches to causality in the context of human research, including neuroimaging studies, meta-analyses of anti-depressant effects of anti-inflammatory drugs, and epigenetic activation of GWAS variants for risks of mental health disorders. I will also explore the hypothetical model that early life adversity and other social stressors could perturb developmental trajectories of the central nervous system and the peripheral immune system, leading to long-term changes in vulnerability to depression and other health disorders in adult life.

Details: Sunday, June 12, 21:00 - 22:00 (GMT+8)

Speaker: Dr. Serena Pudich, Yale University, United States

Chair: Dr. John Krystal, Yale School of Medicine, USA

Description:
Background
During acute COVID-19, patients can experience ischemic cerebrovascular disorders, encephalopathy, and prolonged unconsciousness and altered mental states, including psychosis and delirium. Some individuals also develop a loss of smell and taste, myalgias and fatigue, or neuromuscular disorders. Many patients also experience post-acute COVID neurologic and psychiatric issues. These include prolonged symptoms of fatigue, memory concentration disorder, headache, pain, insomnia, anxiety, and depression.

Aims & Objectives
This talk will cover neurologic reports in acute COVID-19, existing knowledge regarding acute COVID-19 neuropathogenesis, and describe the clinical syndromes and explore potential mechanisms of nervous system Long COVID.

Methods
The speaker will review and critically interpret existing published literature. She will also draw upon her clinical observations and experiences caring for patients with COVID-19 and acute or lingering nervous system consequences. Finally, she will present unpublished data from her group’s investigation into the pathophysiology of Long COVID.

Results
At the end of the talk, the audience should be able to identify the clinical and pathophysiologic effects of SARS-CoV-2 in the nervous system during acute COVID-19, focusing on immunopathogenesis and neuronal injury. The audience will also be able to describe the hypotheses regarding potential underlying mechanisms of nervous system Long COVID, or post-acute sequelae of COVID-19, and recognize that lingering nervous system effects can occur in patients who experienced mild forms of COVID-19.

Discussion
The presentation will conclude with a discussion of future research gaps and priorities particularly with regard to long term neurologic and neuropsychiatric complications post-COVID-19.

Details: Monday, June 13, 3:30 - 4:30 (GMT+8)

Speaker: Dr. Tom Insel, National Institutes of Health, United States

Chair: Prof. Joseph Zohar, Chaim Sheba Medical Center, Israel

Description: Most of us have embarked on careers in neuropharmacology because we want to develop better treatments for people with mental illness and ultimately contribute to public health. Arguably the last five decades have been a golden era for neuropharmacology with a broad range of compounds (as well as psychological and neuromodulatory interventions) developed for mood, anxiety, and psychotic disorders. With so much progress in science, why have we made so little progress in outcomes for people with mental illness, especially those with serious mental illness? Why have we failed to reduce death and disability? Our usual explanations (lack of treatments, lack of knowledge, lack of providers, stigma) are not sufficient answers to this question. We face a mental health crisis not from a failure of research or insufficient workforce but from a broken mental health care system. Fixing the care system through better engagement, quality, and accountability will provide more immediate solutions, including some that can be delivered via technology. In 2022, we can achieve better outcomes from better care, using the treatments we have today. But to close the outcome gap, we need to understand that mental health is not simply a product of mental health care. Indeed, health care explains a relatively small fraction of health outcomes. This presentation will reframe the mental health crisis as more than a healthcare crisis, reminding us that we will always need better treatments but our immediate call to action is to use the treatments we have more effectively.

Details: Friday, June 10, 10:45 - 11:45 (GMT+8)

Speaker: Prof. Joseph Zohar, Chaim Sheba Medical Center, Israel

Description: The current disease-based nomenclature of psychotropics medications does not reflect contemporary knowledge, nor does it appropriately inform the clinician about rational neuroscience-based prescribing. Moreover, it is confusing for the patients as very often we prescribe “antidepressants” for anxiety disorders or “second-generation antipsychotics” to depressed patients who show no evidence of psychosis. Five major international neuropsychopharmacological scientific organizations joined forces together, in 2008, to create new nomenclature. These organizations are: ECNP, ACNP, AsCNP, CINP and IUPHAR.

The mission was:
- To provide a pharmacologically-driven (rather than indication-based nomenclature).
- To expand our toolbox by pointing out the relevant mechanism (via pharmacology and mode of action).
- To help clinicians to make informed choices when they are trying to figure out what would be the next “pharmacological step”.
- To decrease stigma and enhance adherence by a naming system that lays out the rationale for selecting a specific psychotropic.

Currently, NbN has been downloaded close to 100,000 psychiatrists worldwide and has been endorsed by many organizations including APA, EPA, DGPPN, JSPN, and SEP to name a few. It is also a part of major textbook of psychiatry including Oxford textbook of psychiatry, the next edition of Kaplan & Sadock textbook of psychiatry and more. NbN reflects current knowledge and understanding about the targeted neurotransmitters/molecules/system being modified + mode/ mechanism of action and includes 147 compounds that cover the vast majority of psychotropics used worldwide. In this session we will explain the concept and will do live presentation of NbN apps. (IOS: NbN3, NbNca ; Android: NbN3, NbNca).

Details: Saturday, June 11, 13:15 - 14:15 (GMT+8)

Speaker: Prof. Tung Ping Su, Department of Psychiatry, Faculty of Medicine, National Yang Ming Chiao Tung University, Taiwan

Description: Professor Tung-Ping Su has devoted himself to the treatment and research of treatment-resistant depression (TRD) since he returned to Taiwan from the NIMH in the United States in 1996. In Taiwan, he completed the first randomized, double-blind, sham-controlled trial of rTMS in patients with TRD in 2005. He further completed the first randomized, double-blind, placebo-controlled trial of low-dose ketamine infusion in patients with TRD in 2017. His clinical and research career represents the history of novel treatments for TRD in Taiwan. Today, he will talk about the past, present and future of TRD treatment.

Details: Monday, June 13, 00:15 - 01:15 (GMT+8)

Speaker: Prof. Pierre Blier, University of Ottawa Institute of Mental Health Research, Canada

Description: In this workshop, participants will be presented with the various medications that can be used and how to choose the potentially most useful and better-tolerated ones for specific patients. The main interactions with other medications used to treat co-morbidities will be described. Emphasis will be concentrated on cases of treatment resistance and how to devise comprehensive treatment plans. Participants will be encouraged throughout to ask questions and volunteer cases they are currently having difficulties to manage.