Comprehensive Summary
This literature review takes steps to redefine insomnia disorder (ID) as a neurobiological disease of chronic hyperarousal as opposed to its current understanding as a primarily psychiatric disorder. ID is shown to be a multifactorial condition involving persistent cortical excitability, dysregulation of salience and executive control networks, and impaired emotional regulation. This article integrates findings from genetics, neuroimaging, and behavioral neuroscience, revealing that variants in circadian and emotion-related genes such as MEIS1, PER2, and CLOCK interact with early-life stress and adversity through epigenetic mechanisms that shape long-term vulnerability. Neuroimaging studies identify consistent alterations in the orbitofrontal cortex, anterior cingulate, insula, and caudate nucleus, supporting a model of disrupted salience network connectivity underlying sustained arousal. The author reviews current therapies and other treatment modalities including neuromodulatory techniques, pharmacogenetic interventions, and digital therapeutics. This article then demonstrates an understanding of the context of each of these techniques while arguing for their integration into personalized treatment frameworks. This review emphasizes that the pathophysiology of insomnia extends beyond sleep deprivation to involve maladaptive stress responses and emotional hyperreactivity. Cortical beta and gamma overactivity persist during both sleep and wake states, supporting the concept of a 24-hour hyperarousal phenotype. Moving forward, the author advocates for precision neuroscience approaches using EEG and neuroimaging to stratify patients by neurobiological subtype as a step toward optimizing therapeutic outcomes.
Outcomes and Implications
This article makes the argument that insomnia should be elevated to a public health and neuropsychiatric priority, linking it to increased risks of depression, anxiety, cardiovascular disease, and neurodegeneration. Recognizing insomnia as a neuropsychological primary disorder enables earlier identification and more targeted management across medical specialties. The author argues for a biomarker-driven model of precision sleep medicine, integrating neural circuit dysfunction, genetic susceptibility, and environmental stressors into clinical decision-making. Future implementation could include genetic screening for risk alleles, longitudinal phenotyping to monitor stress responsivity, and personalized CBT-I protocols informed by neurocircuit biomarkers. Clinically, this approach encourages replacing one-size-fits-all treatments with more in-depth and individualized regimens combining behavioral therapy, neuromodulation, and pharmacogenomics. The review highlights that chronic insomnia is not merely a lifestyle issue but a disorder of arousal regulation which is often refractory to lifestyle modifications alone, necessitating more extensive means of diagnosis and treatment. This article proposes that with ongoing advances in computational modeling and neural diagnostics, personalized therapeutics for insomnia may transition from research to practice within the next decade.