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and treatment of mental illnesses.

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Circadian Rhythms

RDoC Classification

Domain: Arousal and Regulatory Systems

Description

Circadian Rhythms are endogenous self-sustaining oscillations that organize the timing of biological systems to optimize physiology and behavior, and health. Circadian Rhythms:

  1. Are synchronized by recurring environmental cues;
  2. Anticipate the external environment;
  3. Allow effective response to challenges and opportunities in the physical and social environment;
  4. Modulate homeostasis within the brain and other (central/peripheral) systems, tissues and organs;
  5. Are evident across levels of organization including molecules, cells, circuits, systems, organisms, and social systems.

Molecules

Serotonin

Input

DopamineGABAGlutamateMelanopsinNPYPACAPSubstance P

SCN Synchronizing and Modulating Agents

AVPCalbindincAMPcGMPNOSteroid hormonesVIP

Output

AVPCortisolGABAMelatoninVIP

Cells

FibroblastsipRGCmedium spiny neuronsPars tuberalis cellsPineal cellsrods and conesSCN “clock” cells

Circuits

Input

Raphe to SCN projectionRetinal cellsRetino-hypothalamic tractRetinogeniculate tract

Output

Basolateral amygdala/ HippocampusCentral extended amygdala (central nucleus of the amygdala / Bed nucleus of the stria terminalis)HPA axisHypothalamic neuroendocrine cell groupsHypothalamic orexin projectionsPVN, DMH, subparaventricular zone, PVTSCN/PVN/SCG/pinealSympathetic / parasympathetic nervous system

Intrinsic to SCN

Suprachiasmatic nucleus (SCN) core/shell

Seasonal

SCN/PVN/SCG/pineal

Physiology

Gene expressionNeural activityNeural transmitters

Behavior

Drive-regulated behaviorsLocomotor activityMaskingNeurobehavioral functionsSleep-rated and waking behaviorsSleep-wake

Self-Report

Diary-based measures of daily regularity/ rhythmicity (e.g., Social Rhythm Metric)Morningness-Eveningness QuestionnaireMunich Chronotype QuestionnairePhase, diurnal preference, chronotype (e.g., Horne-Ostberg, CTQ)Sleepiness, alertness, well-being, mood

Paradigms

Dim Light Melatonin Onset (DLMO, phase estimate)Longitudinal Actigraphy

Genetic Approaches – genome-wide association study, candidate gene, epigenomics, circadian genomics (temporal gene expression), mutagenesis, gene targeting, quantitative trait loci.