Circuit-Based Biomarkers for Mood and Anxiety Disorders

Mood and anxiety disorders are complex neural-circuit-based conditions that arise from dysfunctions across multiple cell types, brain regions, and circuits. Recent efforts in identifying circuit-based biomarkers using brain-wide activity patterns have shown promising results in stratifying disorder subtypes and identifying effective treatments for patients with mood and anxiety disorders. Advances in multiregion recording techniques, unbiased data-driven analysis approaches, and machine-learning-based behavioral analysis tools now enable animal studies to effectively reverse translate biomarker-based approaches in human studies to understand how brain-wide activity patterns are altered in disease. The combination of these tools with circuit-based manipulations can help researchers investigate the roles of specific cell types, regions, and circuits in emotional information processing, and how neural circuit dysfunctions manifest in maladaptive behavior. Mood and anxiety disorders are complex heterogeneous syndromes that manifest in dysfunctions across multiple brain regions, cell types, and circuits. Biomarkers using brain-wide activity patterns in humans have proven useful in distinguishing between disorder subtypes and identifying effective treatments. In order to improve biomarker identification, it is crucial to understand the basic circuitry underpinning brain-wide activity patterns. Leveraging a large repertoire of techniques, animal studies have examined roles of specific cell types and circuits in driving maladaptive behavior. Recent advances in multiregion recording techniques, data-driven analysis approaches, and machine-learning-based behavioral analysis tools can further push the boundary of animal studies and bridge the gap with human studies, to assess how brain-wide activity patterns encode and drive emotional behavior. Together, these efforts will allow identifying more precise biomarkers to enhance diagnosis and treatment. Mood and anxiety disorders are complex heterogeneous syndromes that manifest in dysfunctions across multiple brain regions, cell types, and circuits. Biomarkers using brain-wide activity patterns in humans have proven useful in distinguishing between disorder subtypes and identifying effective treatments. In order to improve biomarker identification, it is crucial to understand the basic circuitry underpinning brain-wide activity patterns. Leveraging a large repertoire of techniques, animal studies have examined roles of specific cell types and circuits in driving maladaptive behavior. Recent advances in multiregion recording techniques, data-driven analysis approaches, and machine-learning-based behavioral analysis tools can further push the boundary of animal studies and bridge the gap with human studies, to assess how brain-wide activity patterns encode and drive emotional behavior. Together, these efforts will allow identifying more precise biomarkers to enhance diagnosis and treatment. reduced ability to feel pleasure. In rodents, sucrose preference test is commonly used to assess anhedonia, although it has limited clinical relevance in humans. Instead, subjective self-report questionnaires are more commonly used in humans. a commonly used rodent model of depression, where mice are subjected to daily defeat by aggressive mice (usually of a different strain, such as CD1). Defeated mice exhibit varying degrees of social avoidance, which is used to classify mice as resilient or susceptible to stress. a noninvasive technique to measure brain activity by detecting changes associated with blood flow. an electrophysiological monitoring technique that involves placing electrodes directly on the surface of the brain. transient extracellular electrical signals from large number of surrounding neurons, used as a measure of brain activity. a technique that uses light to control neurons that have been genetically modified to expressive light-sensitive ion channels, allowing temporally and spatially precise circuit manipulations. a type of helplessness behavior, such as immobility, commonly observed in rodents when forced to swim in a space with no escape. a noninvasive brain stimulation technique that involves placing an electromagnetic coil over the scalp. brain activity patterns at resting state in the absence of explicit tasks, usually assessed using fMRI.