Precision Psychiatry 101: Domains

Precision Psychiatry 101 is a four-part series highlighting pillars of Alto’s approach to psychiatric drug development that matches the right patient with the right drug. 

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Precision psychiatry is a rapidly evolving field that seeks to tailor treatments to an individual's unique brain biology. Successfully developing novel precision medicines for mental health conditions first requires a deep understanding of the brain and its neural networks.

The work being done at Alto Neuroscience in identifying and categorizing core domains of mental function – cognition, emotion, and sleep processes – has resulted in a multiple modality approach that supports robust drug-response predictions in mental health. 

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To learn more about the company’s data-driven framework for mapping these domains, see Alto’s publication in Nature Neuroscience which highlights this first-ever, most comprehensive data-driven neurobiological mapping of the human mind.

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Alto has leveraged proprietary approaches, including machine learning-based methods, and other tools to effectively translate how the brain and its mental domains interconnect, in order to efficiently advance the company’s science and pipeline of first- or best-in-class product candidates.

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Cognition 

Cognition, the first core domain of mental function targeted by Alto, allows individuals to perceive, understand, and interact with the world around them, making it an essential aspect of mental health. 

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Cognition involves a range of attributes including attention, working memory, learning, executive function, and neural plasticity. These abilities are critical for daily functioning and are integral to human intelligence. 

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With Alto’s Precision Psychiatry Platform™, the company can both measure these attributes of cognition and target them with new precision medicines for mental health conditions.

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For example, neural plasticity, or the brain’s ability to reorganize itself in response to experiences or changes in the environment, is an essential aspect of cognition that is disrupted in many mental health conditions, including schizophrenia and depression. With a precision psychiatry approach, by directly measuring plasticity and identifying people that may have a deficit in this area, we can better target the disease state by developing drugs that may act in a manner that enhances neural plasticity. 

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Emotion

Emotional processing plays a critical role in mental health – affecting one’s perceptions, behavior, and overall well-being – and emotional disturbances are a common feature of many mental health conditions. 

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Emotion, the second complex and multifaceted domain of mental function Alto is targeting, includes a broad range of experiences – from heightened negative emotion to blunted positive emotion – and relates to aspects of motivation. 

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By measuring the brain circuit underlying emotions with their biomarker platform, Alto aims to better understand how emotional processing affects mental health conditions as the company develops targeted treatments to improve them.

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For example, on a brain circuit level, motivation is influenced by a network of brain structures and neurotransmitters known as the reward system. The reward system impacts a wide range of emotionally-driven behaviors, such as socializing, and is implicated in many mental health conditions including depression and addiction. Through understanding the disruptions in these circuits in certain people, precision psychiatry can be leveraged to influence the underlying cause with specific drugs designed to target the reward system  to improve mental health.

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Sleep

Sleep is a fundamental biological process that is essential for maintaining physical and mental health. Disruptions to sleep are common in many mental health conditions, including depression, anxiety disorders, PTSD, and numerous others.

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This third core domain of mental function encompasses many facets of sleep that are not readily apparent, including circadian rhythms, sleep structure/architecture, sleep duration, and sleep quality. 

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For example, circadian rhythms are biological processes that follow a 24-hour cycle and play a crucial role in regulating sleep-wake cycles, hormone secretion, metabolism, and an individual’s activity patterns. Disruptions to the circadian rhythm, such as those caused by irregular sleep schedules and structure, can have negative effects on physical and mental health. 

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By studying circadian rhythms and other characteristics of sleep, primarily by leveraging data from wearable devices and other tools, Alto is able to identify targets for new therapeutics as well as biomarkers that index these features to better align the treatment with a person’s biology.

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Clinical application 

Alto's identification and categorization of the key domains of mental functioning laid the groundwork for the company's precision psychiatry biomarker platform and advancement of their drug development process.

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As the company works towards matching patients with drugs they are most likely to respond to, clinical data collected on all aspects of cognition, emotion, and sleep will continue to inform future studies, new drug targets, and novel brain biomarkers.