Circuit-Based Biomarkers for Mood and Anxiety Disorders

Abstract

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. Distributed Neural Circuits Underly Mood and Anxiety Disorders Mood and anxiety disorders disrupt basic functions of individuals' lives, and are among the leading causes of disability [1]. In the USA, it is estimated that at a given timepoint, 10-20% of adults are impacted, and 20-30% of adults will experience a mood or anxiety disorder at some point in their lives (https://www.hcp.med.harvard.edu/ncs). However, most existing treatments are not effective [2,3]; largely due to a lack of clear understanding of disease etiology. The search for effective treatment is further complicated by the fact that mood and anxiety disorders are heterogeneous syndromes with various subtypes, where patients present diverse symptoms even for the same disorder, and often respond differently to the same treatment [4-7]. Highlights 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.

Spectral characteristics of subthalamic nucleus local field potentials in Parkinson's disease: Phenotype and movement matter

“…These results also corroborate with the proposal of a possible multivariable framework for adapting DBS strategies, in which a set of features—obtained under specific conditions for specific patients—can outline a customized information processing structure toward an efficient mapping between the set of markers and the required DBS parameters for motor symptoms improvement, in agreement with the current trends in the electrophysiological analysis of circuit‐based pathologies (Xia & Kheirbek, 2020).…”

“…The achieved classification performance was even greater when the combination of phenotype-specific movement-induced desynchronization ranges was used (i.e., 10-20 and 21-28 Hz), capturing, from a machine-learning perspective, the phenotype-movement interaction phenomenon. These results also corroborate with the proposal of a possible multivariable framework for adapting DBS strategies, in which a set of features-obtained under specific conditions for specific patients-can outline a customized information processing structure toward an efficient mapping between the set of markers and the required DBS parameters for motor symptoms improvement, in agreement with the current trends in the electrophysiological analysis of circuit-based pathologies (Xia & Kheirbek, 2020).…”

Threat imminence reveals links among unfolding of anticipatory physiological response, cortical-subcortical intrinsic functional connectivity, and anxiety

“…The copyright holder for this preprint this version posted August 26, 2021. ; https://doi.org/10.1101/2021.08.21.21262409 doi: medRxiv preprint Fourth, we linked this index to specific patterns of functional connectivity that correspond to findings from animal research; this could promote continued cross-species research on circuitbased biomarkers and treatment 118 . Finally, we observed these effects in youth with only anxiety disorders; this suggests specificity as well as potential utility for developmental samples.…”

What Do the Animal Studies of Stress Resilience Teach Us?

“…Such people are classified in psychological research as resilient to stress [ 15 , 17 ]. Over the past few decades, many interesting basic and clinical studies have been conducted to determine the molecular and physiological determinants of depression [ 18 ]. Of these, only a handful of experiments have attempted to elucidate the biochemical mechanisms underlying psychological stress resilience in humans.…”