Introduction
Anxiety is the most common mental health disorder worldwide with a global prevalence of ∼25% [1], and is characterized by inflated and persistent feelings of fear and worry that are out of proportion to the actual threat, with impaired daily functioning [2,3]. Common anxiety disorders include generalized anxiety disorder (GAD), panic disorder (PD), specific phobias, agoraphobia, social anxiety disorder (SAD), and separation anxiety disorder [2]. Furthermore, anxiety-related disorders formerly classified anxiety disorders and no longer listed as such according to the Diagnostic and Statistical Manual (DSM-5) [2] include post-traumatic stress disorder (PTSD), obsessive-compulsive disorder (OCD), adjustment disorder and selective mutism (more common in children) (see Table 1 for a list of anxiety/anxiety-related disorders and their main symptoms).
Individuals with anxiety/anxiety-related disorders often experience poor sleep quality, and exhibit sleep disturbances, particularly insomnia [4]. Conversely, insufficient sleep can instigate or further exacerbate anxiety [5]. Neuroimaging studies using functional magnetic resonance imaging (fMRI) indicate that total sleep loss amplifies activity within the “fear network”, which includes the limbic system [[6], [7], [8]] and the salience network involved in cognitive control (dorsal anterior cingulate cortex and anterior insula) [9]. Furthermore, the anxiogenic impact of total sleep loss relates to impaired medial prefrontal cortex activity and associated connectivity with extended limbic regions [10]. Growing molecular imaging evidence posits that specific neurotransmitter mechanisms underlying sleep-wake regulation, like the adenosinergic system, are involved in anxiety [∗[11], [12], ∗[13], [14]]. Together, these findings suggest a key contribution of sleep-arousal systems in anxiety/anxiety-related disorders (see Fig. 1 for a schematic). Current frontline treatments for anxiety/anxiety-related disorders oftentimes target sleep disturbances, particularly insomnia, by using single or combined strategies as nonbenzodiazepines and/or antidepressants [15], lifestyle interventions [16] and cognitive behavioral therapy for insomnia (CBT-I) [17,18]. Despite therapeutic success, up to a third of individuals experiencing e.g., anxiety-related disorders (OCD, PTSD) do not sufficiently respond to frontline treatments [19,20]. A promising target for improving anxiety symptoms are slow wave sleep (SWS) and slow wave activity (SWA; EEG power density in the frequency range of ∼0.5–4 Hz), which are the primary markers of sleep homeostasis. FMRI findings indicate that slow wave oscillations offer an ameliorating, anxiolytic benefit on brain networks (e.g., limbic system) following sleep [10]. Hence, there is strong interest for novel non-invasive brain stimulation (NIBS) techniques that can induce SWS/SWA [[21], ∗[22], [23]]. As individuals with anxiety/anxiety-related disorders may exhibit less SWS [24], these alternative approaches may translate to new evidence-based treatment strategies that have the potential to alleviate sleep and anxiety symptoms.
The goal of our narrative review is to address and foster an important debate on the interrelationship between sleep and anxiety, provide a comprehensive overview of recently identified brain and cortical receptor mechanisms implicated in this two-way crossroad, and address novel evidence-based sleep interventions to enhance sleep quality, thereby improving anxiety in individuals who experience this common ailment.