Abstract
The mood disorder prodrome is conceptualized as a symptomatic, but not yet clinically diagnosable stage of an affective disorder. Although a growing area, more focused research is needed in the pediatric population to better characterize psychopathological symptoms and biological markers that can reliably identify this very early stage in the evolution of mood disorder pathology. Such information will facilitate early prevention and intervention, which has the potential to affect a person’s disease course. This review focuses on the prodromal characteristics, risk factors, and neurobiological mechanisms of mood disorders. In particular, we consider the influence of early-life stress, inflammation, and allostatic load in mediating neural mechanisms of neuroprogression. These inherently modifiable factors have known neuroadaptive and neurodegenerative implications, and consequently may provide useful biomarker targets. Identification of these factors early in the course of the disease will accordingly allow for the introduction of early interventions which augment an individual’s capacity for psychological resilience through maintenance of synaptic integrity and cellular resilience. A targeted and complementary approach to boosting both psychological and physiological resilience simultaneously during the prodromal stage of mood disorder pathology has the greatest promise for optimizing the neurodevelopmental potential of those individuals at risk of disabling mood disorders.
Highlights
There is increasing appreciation for the need to both identify and treat mood disorders during their earliest stages [1]
The potential to intervene during the prodromal stage of psychiatric illness through the detection and remediation of novel biomarkers has perhaps been best studied in schizophrenia, wherein most individuals experience a lengthy prodromal period prior to the full emergence of diagnosable psychotic symptoms [6]
Biomarkers that characterize the level of neuronal vulnerability relative to resilience may prove useful as biomarkers of prodromal mood disorder pathology. This has been demonstrated for later stages of bipolar disorder [84], more studies are needed to determine the utility of such cell danger biomarkers during the mood disorder prodrome [22]
Summary
There is increasing appreciation for the need to both identify and treat mood disorders during their earliest stages [1]. Observable changes in mood and general physiologic functioning can include increases in sadness, anhedonia, irritability, anger, and anxiety, together with alterations in sleep and energy [4] Correlating these symptoms with prodromal biomarkers offers an exciting juncture whereby targeted interventions could be opportunistically employed to prevent neurodegenerative changes from accruing as the disease progresses [5]. Encouraging results from this work have renewed interest in the early detection of affective disorders, bipolar disorder, with the hope that earlier and more targeted interventions might slow disease progression [3, 9,10,11,12] This can significantly impact neuroprogression and subsequent disease course for the individual [13]. This process results from disturbances in inflammatory mediators, neurotrophins, oxidative stress, and energy regulation [14, 15]
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