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191 - Revolutionizing our understanding of mental illness with optogenetics — Whalespan

Content›Video›191 - Revolutionizing our un…

191 - Revolutionizing our understanding of mental illness with optogenetics

Peter Attia2h 42m · 2022-01-17

Claims Made

191

Claims Supported

137

Support Rate

72%

Support rate

137 of 191 claims supported

137 supported54 partial / not

Claims from this content

98

✓Well SupportedAutism is highly heritable, estimated at 85-90%, with underlying genetic factors potentially differing among affected children.✓Well SupportedAnhedonia, the absence of pleasure, is a core symptom of depression and can lead to a diagnosis of major depressive disorder.✓Well SupportedDifferent cell populations in the brain control distinct features of anxiety, including breathing changes, behavioral avoidance, and negative subjective state.✓Well SupportedHeritability for bipolar disorder and schizophrenia is approximately 0.5 to 0.6, and for major depression, it is around 0.3.Well Supported

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A. Volkovreader

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Bookmarking — the dossier-vs-overview split is the right call. Most of the time I want overview; sometimes I want receipts.

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Bipolar type one disorder is an extraordinarily genetically determined psychiatric disorder with concordance rates in identical twins raised apart exceeding 70%.

◐Partially SupportedActivating dopamine neurons with laser light can create a preference for a specific location, analogous to a reward stimulus like sugar water or cocaine.

◐Partially SupportedUnderstanding specific cell types involved in social interaction deficits in autism could enable targeted medication design.

◐Partially SupportedBenzodiazepine medications can help manage anxiety in patients with autism spectrum disorder but do not address social deficits.

◐Partially SupportedAnxiety involves behavioral avoidance, physiological changes, and a negative subjective feeling.

◐Partially SupportedAnxiety is a normal and appropriate feeling, with diagnosis dependent on the degree of impairment it causes to function.

✓Well SupportedOptogenetics is crucial for establishing a causal understanding of brain activity patterns and their link to specific symptoms.

◐Partially SupportedThe mouse cortex is remarkably similar to the human cortex, possessing the same six layers and types of neurons connected in the same manner.

◐Partially SupportedMania is characterized by elevated mood, increased goal-directed activity, faster speech, and a reduced need for sleep.

◐Partially SupportedThe motivation to immigrate may be genetically linked to recent immigrants.

◐Partially SupportedMutations in genes linked to autism can impair social interaction in mice, serving as models for studying the disorder.

✓Well SupportedOptogenetics is a tool for precise targeting of specific cell types that was quickly appreciated by psychiatrists interested in the science side.

◐Partially SupportedA normal mammalian neuron's action potential can be triggered by signals in the order of 100 to 200 picoamps.

◐Partially SupportedAnimal behavior in conditioned place preference/aversion tests can report the positive or negative valence of an experience.

◐Partially SupportedSpecific dopamine neurons may increase the drive for social interaction, while cells in the frontal cortex might be more involved in processing cognitive aspects of social information in individuals with autism.

◐Partially SupportedMania can be triggered by context and manifest as sustained elevated mood and energy, driving significant risks and life shifts.

◐Partially SupportedViral injection into a specific brain region creates a localized 'hot spot' for gene delivery.

◐Partially SupportedElectroconvulsive therapy (ECT) is a highly effective treatment for treatment-resistant depression.

◐Partially SupportedViral injections primarily infect cell bodies in a region, offering more specificity than electrodes which stimulate all passing axons.

◐Partially SupportedExposure to patients with acute schizophrenia or schizoaffective disorder in a locked psychiatric ward provides a clear expression of symptoms.

◐Partially SupportedEarly life trauma has lasting psychiatric influence throughout life and can cause severe problems, including personality disorders.

◐Partially SupportedEarly life trauma can cause adaptive changes in brain circuitry, leading to expectations of a harsh world.

◐Partially SupportedEarly life trauma can lead to lasting states of depression by establishing a value system that anticipates aversive outcomes.

◐Partially SupportedEmotional tears may result from minor rewiring in the brainstem connecting emotional regions to tear duct control.

◐Partially SupportedPeter Attia can help manage anxiety in patients with autism spectrum disorders with medications like benzodiazepines.

◐Partially SupportedAnxiety disorders are the most common psychiatric disorders when grouped together.

◐Partially SupportedAnxiety becomes a psychiatric disorder when it exceeds a healthy range.

◐Partially SupportedAnxiety is closely associated with autism spectrum disorder.

◐Partially SupportedExploiting promoters and enhancers of cell-type specific enzymes, like those for dopamine synthesis, allows for cell-type specific gene expression.

◐Partially SupportedPromoters and enhancers are DNA sequences that attract transcription factors to regulate gene expression.

◐Partially SupportedGene expression can be altered throughout life, potentially explaining lasting effects of early life experiences without changing the genome.

◐Partially SupportedIntroducing genes into neurons was technically challenging until the late 1990s due to a lack of effective methods.

◐Partially SupportedViruses are evolved to efficiently introduce genetic material into cells.

◐Partially SupportedAnimals will prefer a location where a specific neuron has been activated by laser light compared to an identical location without activation.

◐Partially SupportedMicrobial opsins were key to the development of optogenetics.

◐Partially SupportedECT has side effects and is not a permanent fix, with some patients requiring maintenance ECT every three months to sustain the effect.

◐Partially SupportedCrude methods to inhibit neuronal firing, such as exhausting cells with strong electrical stimulation, lack cell-type specificity.

◐Partially SupportedThe mechanisms of action for current psychiatric treatments and medications are not fully understood.

◐Partially SupportedAnxiety is a significant factor in depression and autism spectrum disorders.

◐Partially SupportedOptogenetics has provided insights into the neural pathways and neurotransmitters involved in anhedonia.

◐Partially SupportedStressed or sleep-disrupted rodents show a reduced preference for sugar water, indicating a loss of interest in normally rewarding stimuli.

◐Partially SupportedIn rodents, overactivity in prefrontal cortical areas can lead to anhedonia by impairing dopamine neurons' ability to recruit reward circuitry.

◐Partially SupportedAn overactive frontal cortex can suppress positive aspects, contributing to anhedonia.

◐Partially SupportedDepression may be an evolutionarily adaptive form of energy conservation.

◐Partially SupportedPsychiatric diagnoses cannot yet be made based on biomarkers, relying instead on patient-reported questions.

◐Partially SupportedDepression can be characterized by a removal of joy, energy, and reward-seeking drive, leading to passivity.

◐Partially SupportedEarly psychiatric practice lacked specific tools and techniques to target particular cell types, leading to non-specific treatments.

◐Partially SupportedThe origins of depression and anxiety are not well understood, and current treatments lack cell-type specificity.

◐Partially SupportedThe reason why depression feels like agony or psychic pain, driving suicidal ideation, is not understood.

✕Not SupportedCurrent clinical therapies for depression lack a precise understanding of the underlying biological mechanisms.

✕Not SupportedIndividuals are at increased risk of self-harm during a manic phase or during the transition from depression to mania.

◐Partially SupportedInformation flows through the brain via an electrochemical process where electrical impulses trigger chemical releases across synapses, which then create new electrical impulses in downstream cells.

◐Partially SupportedThe human brain contains approximately 90 billion neurons.

◐Partially SupportedTranscranial magnetic stimulation (TMS) in its early stages produced small effects at the population level and its mechanism is not fully understood.

◐Partially SupportedEngineering viral capsids to target specific cell surface proteins could create a lock-and-key mechanism for cell-type specific gene delivery.

◐Partially SupportedElectrical stimulation of the brain with electrodes lacks cell-type specificity.

◐Partially SupportedGiving up on an inescapable, challenging situation is a form of hopelessness that involves discounting effort and can be an adaptive coping mechanism by conserving energy and reducing risk.

◐Partially SupportedDNA contains the genetic code, a sequence of nucleotides (A, G, C, T), that dictates the production of specific proteins.

✕Not SupportedMania can lead to serious problems, including poor decision-making and potentially fatal outcomes.

◐Partially SupportedMedications can help somewhat with medical conditions, but they do not provide understanding of the underlying causes.

◐Partially SupportedMicrobial opsins generate tiny currents, which may have contributed to researcher hesitancy in adopting them for neurostimulation compared to mammalian ion channels.

◐Partially SupportedViruses introduce genetic material into cells to trigger the creation of new virus particles for replication and spread.

◐Partially SupportedScientists test both the sufficiency and necessity of biological components to understand their function.

◐Partially SupportedThe technology for introducing genes into neurons using safe, modified viruses has become more feasible.

◐Partially SupportedThe dose of viral particles administered determines the number of cells that will pick up a gene and the number of gene copies per cell.

◐Partially SupportedModified viruses can be used to introduce DNA into cells for research purposes.

◐Partially SupportedRNA serves as an intermediate step between DNA and protein synthesis.

◐Partially SupportedFrancis Crick suggested in 1999 that light could be a suitable method for achieving cell-type specificity in neurostimulation due to its speed, relative non-invasiveness, scattering properties, and the fact that most neurons do not respond to light at baseline.

◐Partially SupportedOptogenetics allows for the precise introduction of genes into specific cell types, enabling the use of photons to control neuronal activity.

◐Partially SupportedThe brain is an immune-privileged organ where T cells and B cells do not have free access.

◐Partially SupportedSome dopamine neurons can release glutamate, while others can release GABA.

◐Partially SupportedNeurons can release multiple neurotransmitters simultaneously, including neuropeptides.

◐Partially SupportedA patient with neglect syndrome after a thalamic infarct was unable to draw a complete clock.

?Limited ResearchThe exact mechanism for the cyclical nature of bipolar disorder is not yet understood.

◐Partially SupportedAnxiety has physiological, behavioral, and subjective valence components.

✕Not SupportedBenzodiazepines are effective anti-anxiety medications but can be addictive, lead to dose adaptation, and cause cognitive slowing and sedation.

?Limited ResearchThe specific neurons targeted by anti-anxiety medications like benzodiazepines are not yet precisely known, hindering the development of more targeted interventions.

◐Partially SupportedThe first paper using a microbial opsin for light sensitivity in neurons was published in the summer of 2005.

◐Partially SupportedBenzodiazepines facilitate the action of inhibitory GABA receptors.

◐Partially SupportedPreference strength in mice for a location can be increased or decreased by making the experience more extreme.

◐Partially SupportedOptogenetics can restore sight by creating light sensitivity in degenerated retinas.

◐Partially SupportedOptogenetics offers a potential ten-year time scale for developing autism treatments.

◐Partially SupportedMice can behaviorally report whether something has positive or negative value to them.

◐Partially SupportedMice will prefer one chamber over another approximately 70-80% of the time with typical rewards.

◐Partially SupportedOptogenetics can control human retinal neurons in vitro for vision restoration.

◐Partially SupportedStimulating dopamine neurons optogenetically is unequivocally positive.

◐Partially SupportedPeripheral optogenetics can lead to loss of opsin expression in cells over months, partly due to immune response.

◐Partially SupportedDeep brain structures like the hypothalamus, which govern primary needs such as salt balance, danger avoidance, mating, sleeping, and thermoregulation, are common to and shared among all vertebrates.

◐Partially SupportedDifferent cells have diverse receptors that can respond to the same neurotransmitter in different ways.

◐Partially SupportedUsing a tyrosine hydroxylase promoter with channelrhodopsin allows opsin expression specifically in dopamine cells.

◐Partially SupportedLocal injection of viruses for gene therapy is often preferred over systemic administration due to cost-effectiveness and cell-type specificity.

◐Partially SupportedAdenoviruses replicate by incorporating genetic material into host cell machinery, which is recognized by the immune system.

◐Partially SupportedViral technologies can deliver hundreds or more copies of a gene per cell, enabling larger currents from microbial opsins compared to existing methods that deliver one to seven copies.

◐Partially SupportedAchieving cell-type specificity for opsin production is necessary because different cell types are jumbled together in the same brain regions.