Orexin/Hypocretin System Dysfunction in ESSENCE (Early Symptomatic Syndromes Eliciting Neurodevelopmental Clinical Examinations)

Abstract

Early Symptomatic Syndromes Eliciting Neurodevelopmental Clinical Examinations (ESSENCE) is an umbrella term covering a wide range of neurodevelopmental difficulties and disorders. Thus, ESSENCE includes attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and other neurodevelopmental disorders (NDDs) and difficulties, with a variety of symptoms in cognitive, motor, sensory, social, arousal, regulatory, emotional, and behavioral developmental domains, frequently co-occurring and likely having partly common neurobiological substrates. The ESSENCE concept is a clinical paradigm that promotes organizing NDDs in everyday clinical practice according to their coexistence, symptom dimensions overlapping, and treatment possibilities. Despite increased knowledge regarding NDDs, the neurobiological mechanisms that underlie them and other ESSENCE-related problems, are not well understood. With its wide range of neural circuits and interactions with numerous neurotransmitters, the orexin/hypocretin system (Orx-S) is possibly associated with a variety of neurocognitive, psychobiological, neuroendocrine, and physiological functions and behaviors. Dysfunction of Orx-S has been implicated in various psychiatric and neurological disorders. This article provides an overview of Orx-S dysfunctions' possible involvement in the development, presentation, and maintenance of ESSENCE. We provide a focused review of current research evidence linking orexin neuropeptides with specific clinical NDDs symptoms, mostly in ADHD and ASD, within the Research Domain Criteria (RDoC) framework. We propose that Orx-S dysfunction might have an important role in some of these neurodevelopmental symptom domains, such as arousal, wakefulness, sleep, motor and sensory processing, mood and emotional regulation, fear processing, reward, feeding, attention, executive functions, and sociability. Our perspective is presented from a clinical point of view. Further, more thorough systematic reviews are needed as well as planning of extensive new research into the Orx-S’s role in ESSENCE, especially considering RDoC elements.

Keywords:

• attention-deficit/hyperactivity disorder
• autism spectrum disorder
• developmental coordination disorder
• neurodevelopmental disorders
• research domain criteria
• orexin
• hypocretin

Abbreviations

AD, Alzheimer's Disease; ADHD, Attention-Deficit/Hyperactivity Disorder; AN, Anorexia Nervosa; ARFID, Avoidant Restrictive Food Intake Disorder; ASD, Autism Spectrum Disorder; ASLO, Anti-Streptolysin O; BPS, Behavioral Phenotype Syndromes; CFS, Chronic Fatigue Syndrome; COVID-19, Coronavirus Disease 2019; DCD, Developmental Coordination Disorder; DSED, Disinhibited Social Engagement Disorder; ESSENCE, Early Symptomatic Syndromes Eliciting Neurodevelopmental Clinical Examinations; FAS, Fetal Alcohol Syndrome; FASD, Fetal Alcohol Spectrum Disorder; GABA, Gamma-Aminobutyric Acid; GAD65, Glutamic Acid Decarboxylase 65; hEDS, Hypermobile Ehlers-Danlos Syndrome; HLA, Human Leukocyte Antigen; HPA, Hypothalamus-Pituitary-Adrenal; HRV, Heart rate variability; HSD, Hypermobility Spectrum Disorder; LH, Lateral Hypothalamus; ME, Myalgic Encephalomyelitis; NDD, Neurodevelopmental Disorder; NT1, Narcolepsy Type 1; OCD, Obsessive-Compulsive Disorder; ODD, Oppositional-Defiant Disorder; Orx-A, Orexin-A/Hypocretin-1; Orx-B, Orexin-B/Hypocretin-2; Orx1R, Orexin/Hypocretin Type 1 Receptor; Orx2R, Orexin/Hypocretin Type 1 Receptor; Orx-S, Orexin/Hypocretin System; PANDAS, Paediatric Acute-Onset Neuropsychiatric Disorder Associated with Streptococcal Infection; PANS, Pediatric Acute-Onset Neuropsychiatric Syndrome; RAD, Reactive Attachment Disorder; RDoC, Research Domain Criteria; VLPO, Ventrolateral Preoptic.

Disclosure

The authors report no conflicts of interest in this work.