Epidemiological characteristics of comorbidities in childhood Attention-Deficit/Hyperactivity Disorder and common comorbidity patterns.

Sleep is a fundamental biological process that is essential for maintaining physical health, cognitive performance, and psychological well-being. Increasing evidence suggests that sleep disorders are associated with a range of neurological and psychiatric conditions, emphasizing the importance of understanding their underlying mechanisms [,]. One extensively studied sleep disorder is obstructive sleep apnea syndrome (OSAS). It is diagnosed primarily by overnight polysomnography and is commonly defined by an apnea-hypopnea index (AHI) of ≥5 events/hour in symptomatic individuals or ≥15 events/hour irrespective of symptoms. The disorder typically presents with loud snoring, witnessed apneic episodes, nocturnal gasping or choking, excessive daytime sleepiness, morning headaches, impaired concentration, and reduced quality of life. OSAS disrupts the sleep cycle that consists of three main stages: N1 and N2, known as light sleep; N3, called deep sleep; and rapid eye movement (REM) sleep, which is also known as vivid dreaming, crucial for physical restoration, memory consolidation, and cognitive function []. OSAS disrupts normal sleep architecture through recurrent arousals, reducing both REM sleep continuity and slow-wave (N3) sleep, thereby impairing restorative sleep and cognitive recovery []. OSAS is characterized by recurrent upper airway obstruction during sleep, resulting in intermittent hypoxia (IH), recurrent arousals, and sleep fragmentation (SF), which have been associated with an increased risk of cardiovascular and neurodegenerative disorders [,,,]. Obstructive sleep apnea syndrome is one of the most common sleep-related breathing disorders and represents a significant global public health concern. Epidemiological studies suggest that its prevalence increases with age, obesity, and male sex, while a substantial proportion of affected individuals remain undiagnosed worldwide []. Although OSAS may occur at any age, it is most prevalent among middle-aged and older adults, while children and younger adults may also be affected, particularly in the presence of adenotonsillar hypertrophy, craniofacial abnormalities, or obesity []. There is also widespread evidence of excessive daytime sleepiness, unstable interpersonal relationships, increased road traffic accidents, and reduced productivity at work and impaired academic performance in children and adolescents, resulting in poor quality of life for patients [,]. Neuropsychiatric comorbidities are also common among individuals with OSAS. Previous studies have consistently reported a higher prevalence of depression, anxiety, and cognitive impairment in patients with OSAS than in the general population [,]. Collectively, these observations provide a compelling rationale for exploring how OSAS may contribute to neuropsychiatric disorders through neuroinflammatory mechanisms. Recent research in sleep medicine and neuroimmunology suggests that the neurological consequences of OSAS extend beyond sleep disruption alone. Recurrent intermittent hypoxia and sleep fragmentation are associated with oxidative stress, systemic inflammation, and vascular dysfunction [,,]. Higher levels of inflammatory biomarkers, including interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP), have been consistently reported in patients with OSAS. These inflammatory processes may contribute to blood-brain barrier (BBB) dysfunction, activation of microglia and astrocytes, and neuronal injury, providing a potential mechanistic link between OSAS and cognitive and emotional dysfunction []. Collectively, these findings suggest that neuroinflammation may represent an important mechanistic link between OSAS and long-term cognitive and emotional dysfunction [,,,,]. Neuroinflammation has emerged as a potential mechanism linking OSAS with cognitive decline and mood disturbances. The evolving changes in sleep cycles and quality in patients with OSAS, along with altered cerebral blood flow and neurotransmitter activity, contribute to impaired neuroplasticity, vaso-neural alterations, and disruption of cellular redox reactions. This then leads to oxidative stress through repeated nocturnal hypoxemia and SF, which remain under scrutiny [,,]. This neural injury can lead to a range of dysfunctions, including emotional changes, cognitive decline, loss of sensation, and motor disturbances [,,]. In addition, these pathological processes are implicated in the development of neurodegenerative disorders such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) [,,,]. Accumulating evidence suggests that intermittent hypoxia may contribute to neuroinflammatory and neurodegenerative processes through mechanisms including oxidative stress, blood-brain barrier dysfunction, glial activation, and inflammatory cytokine release. Although these mechanisms are increasingly recognized, the extent to which they contribute to long-term neuropsychiatric and neurodegenerative outcomes remains