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editorial
. 2024 Jan 9;47(3):zsad330. doi: 10.1093/sleep/zsad330

Unraveling the complex interplay between insomnia, anxiety, and brain networks

Tianxin Mao 1, Bowen Guo 2, Hengyi Rao 3,4,5,
PMCID: PMC10925950  PMID: 38195150

Sleep plays a paramount role in human health, yet billions of people worldwide grapple with inadequate sleep or sleep disorders. Among these, insomnia emerges as the most prevalent sleep disorder and ranks as the second most common neuropsychiatric disorder [1, 2]. Approximately 10% of adults contend with an insomnia disorder, while an additional 20% experience intermittent insomnia symptoms. Often assuming a chronic trajectory, insomnia exhibits a 40% persistence rate over a 5-year span [3]. Chronic insomnia disorder (CID), ubiquitous in the general population and frequently encountered in clinical settings, poses substantial threats to individual academic attainment, quality of life, safety, as well as mental and physical well-being [4–7]. CID also imposes a noteworthy economic impacts, manifested in both direct treatment expenses and indirect costs arising from increased work absenteeism and diminished productivity [3].

CID frequently coexists with anxiety, the predominant category of mental disorders characterized by excessive fear, anxiety, or avoidance of perceived threats [8, 9]. Conversely, nearly three-quarters of participants with anxiety disorder reported sleep disturbances [10], demonstrating a bidirectional relationship between insomnia and anxiety. Longitudinal investigations further reveal that insomnia often precedes the onset of anxiety disorders, suggesting a potential causal link [11]. Additionally, some studies suggest that insomnia and disrupted sleep may serve as indicators of disrupted neuroplasticity in mood disorders [12–15], while other research proposes that persistent anxiety symptoms may exacerbate or trigger insomnia [16]. Consequently, a detrimental cycle ensues, wherein insomnia and anxiety symptoms mutually influence each other.

Numerous studies have examined the neural underpinnings of insomnia and anxiety, revealing shared brain networks between them. For instance, alterations in the hypothalamic-pituitary-adrenal network, commonly observed in anxiety disorders, are frequently implicated in disruptions of sleep regulation [17]. The hyper-arousal theory posits that individuals with anxiety disorders experience heightened brain activity, disrupting sleep patterns [18]. Additionally, sleep deprivation impacts brain networks, leading to increased anxiety, and this relationship may be mediated by the adenosinergic neurotransmitter system [9]. Specifically, insomnia is intricately linked with the default mode network, salience network, executive control network, ventral attention network, and subcortical regions such as the thalamus and hypothalamus [19–24]. In contrast, anxiety also exhibits intricate associations with the default mode network, ventral attention network, fronto-parietal network, and cingulo-opercular network [25–27]. The default mode network plays a crucial role in self-referential thinking and is associated with rumination, having been implicated in the pathophysiology of both insomnia and anxiety [21, 28]. While these studies revealed the commonalities between insomnia and anxiety, they did not concurrently address their shared and distinct features and characteristics, leaving the underlying neurobiology of insomnia and anxiety yet to be fully comprehended.

In the current issue of SLEEP, Shen et al. employed resting-state functional MRI and functional connectivity density mapping approaches to identify common and distinct brain network abnormalities in a relatively large cohort of 130 patients with CID, as compared to 50 good sleep controls [29]. Patients with CID were stratified into anxious (CID-A) and non-anxious (CID-NA) subgroups based on Self-rating Anxiety Scale (SAS) scores. Behavioral results corroborated the relationship between insomnia and anxiety in terms of rumination [30, 31]. Imaging results revealed shared functional connectivity and functional connectivity density changes in CID-A and CID-NA patients. Interestingly, only the CID-A group exhibited altered long-range functional connectivity density in the precuneus and disrupted default mode network functional connectivity. Furthermore, deficits in default mode network function mediate the relationship between insomnia and anxiety severity. These findings offer neurological evidence for Harvey’s widely cited cognitive model of insomnia [32], and may guide the development of more specific and effective treatment strategies for insomnia patients with and without anxiety, for example through cognitive behavior therapy and neuromodulation interventions.

As discussed before, patients with insomnia frequently manifest anxiety symptoms to some extent, creating a challenge in disentangling insomnia from anxiety. In this study [29], patients with CID were stratified into anxious and non-anxious subgroups based on SAS scores. Nevertheless, noteworthy differences in SAS scores persisted between the healthy controls and CID-NA groups. Future studies may benefit from including a healthy control group with SAS scores similar to those of the CID-NA group to more effectively distinguish between insomnia and anxiety. Moreover, the CID-NA and CID-A groups exhibited significant disparities in age, insomnia severity, and depression scale, in addition to anxiety. Such variations may potentially compromise the validity of the study results. In order to bolster the robustness of future investigations, it is imperative to devise a more nuanced experimental design that considers comprehensive criteria and employs sophisticated statistical techniques to control for potential confounding factors.

While statistical models can provide valuable insights into the neural mechanisms connecting insomnia and anxiety, the establishment of causality remains inconclusive based on the current study [29]. To address this limitation, future research should consider conducting longitudinal studies with substantial sample sizes, aiming to track brain activity and connectivity changes over time in individuals affected by both insomnia and anxiety. Future research may also broaden the scope by examining anxious patients with and without insomnia symptoms, which can offer a more comprehensive understanding of the neurobiological underpinnings of these conditions. In addition, the circuits identified in this study could be targeted with treatments such as transcranial magnetic stimulation and deep brain stimulation to provide evidence for the causal relationship [33, 34]. Implementing these approaches will contribute to an expanded understanding of the causal relationship between insomnia and anxiety.

The brain functions as a complex integrative network, where functionally linked regions sustain a continual exchange of information, collectively forming interconnected resting-state communities [35, 36]. An alternative analytical method, specifically large-scale brain network analysis that emphasizes connectivity among key nodes, may provide additional evidence regarding the role of default mode network in the interplay between insomnia and anxiety. Moreover, the study’s concentration on functional connectivity prompts consideration of exploring structural connectivity in future investigations, offering deeper insights into the topic. For instance, numerous tractography studies on insomnia disorder have consistently reported decreased structural connectivity between cortical and subcortical structures [22, 37–39]. Therefore, incorporating an exploration of large-scale brain network analysis and structural connectivity may enrich our understanding of the intricate relationship between insomnia and anxiety. Additionally, the integration of neuroimaging with other biometric data, such as genetic information and biomarkers, holds promise for achieving a more holistic understanding of these disorders.

In summary, the complex and bidirectional relationship between insomnia and anxiety remains a pivotal area of research in mental health and behavioral medicine. Findings from this study by Shen et al. provide a potential biological framework for understanding the interplay among sleep, anxiety, and brain networks. The identification of deficits in the default mode network aligns with the growing interest in noninvasive neural stimulation approach that may directly target brain network connectivity. Looking forward, the cooperation of multidisciplinary experts, the establishment of standardized protocols, and the utilization of shared databases are necessary to transform research findings into clinical practice and alleviate the great burden of highly prevalent insomnia and anxiety.

Contributor Information

Tianxin Mao, Center for Magnetic Resonance Imaging Research and Key Laboratory of Brain-Machine Intelligence for Information Behavior (Ministry of Education and Shanghai), School of Business and Management, Shanghai International Studies University, Shanghai, China.

Bowen Guo, Center for Magnetic Resonance Imaging Research and Key Laboratory of Brain-Machine Intelligence for Information Behavior (Ministry of Education and Shanghai), School of Business and Management, Shanghai International Studies University, Shanghai, China.

Hengyi Rao, Center for Magnetic Resonance Imaging Research and Key Laboratory of Brain-Machine Intelligence for Information Behavior (Ministry of Education and Shanghai), School of Business and Management, Shanghai International Studies University, Shanghai, China; Center for Functional Neuroimaging, Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA; Unit for Experimental Psychiatry, Division of Sleep and Chronobiology, Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA.

Disclosure Statement

None.

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