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The National Institute of Mental Health (NIMH) Research Domain Criteria (RDoC) has provided a framework for conceptualizing symptomatology across circuits and structures rather than disease states. By re-orienting research away from traditional diagnostic categories towards a multimodal dimensional framework, ...

The National Institute of Mental Health (NIMH) Research Domain Criteria (RDoC) has provided a framework for conceptualizing symptomatology across circuits and structures rather than disease states. By re-orienting research away from traditional diagnostic categories towards a multimodal dimensional framework, it will lend to the develop a scientific base that can inform future neuroscience-based diagnostic systems for mental illness. The positive valence system (PVS) also referred to as appetitive or approach motivation has been introduced as a domain focused on reward-seeking behaviors and is related to a subgroup of symptoms characterized by motivational deficits and abnormalities. Motivational dysfunctions are a core feature of several neuropsychiatric disorders, including schizophrenia, depression, substance use disorder, Parkinson’s disease, and overeating. Positive valence symptoms are predictive of therapeutic response and are not readily treated by current pharmacotherapies; therefore, elucidating the neurocircuitry underlying these symptoms is critical for symptom relief and treatment.

Identifying pathophysiological mechanisms underlying transdiagnostic symptom clusters can help break down potentially arbitrary distinctions between categorically defined psychiatric disorders and account for comorbidity among current diagnostic categories. The purpose of this series of articles is to critically review molecules, circuits and physiology involved in the pathophysiology of positive valence systems by addressing the following subtopics:

1. Down-regulation or deactivation of motivational circuitry leads to decreased motivation and goal-related behavior
2. Relationship between different symptom terms lassitude, psychomotor slowing, fatigue, apathy, anergia
3. Fatigue Parkinson’s Disease
4. Negative Symptoms of Schizophrenia
5. Animal Models for Drug Development

Keywords: Psychomotor slowing, Apathy, Reward Processing, Fatigue, Anergia


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