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Insomnia and restless leg syndrome (RLS) are associated with increased risk for suicidal behavior (SB), which is often comorbid with mood or thought disorders; however, it is unclear whether these relationships are causal. We performed a two-sample Mendelian randomization study using summary-level genetic associations with insomnia symptoms and RLS against the outcomes of risk of major depressive disorder (MDD), bipolar disorder (BP), schizophrenia (SCZ), and SB. The inverse-variance weighted method was used in the main analysis. We performed replication and sensitivity analyses to examine the robustness of the results. We identified outcome cohorts for MDD (n = 170,756 cases/329,443 controls), BP (n = 20,352/31,358), SCZ (n = 69,369/236,642), SB-Cohort-2019 (n = 6569/14,996 all with MDD, BP or SCZ; and SB within individual disease categories), and SB-Cohort-2020 (n = 29,782/519,961). Genetically proxied liability to insomnia symptoms significantly associated with increased risk of MDD (odds ratio (OR) = 1.23, 95% confidence interval (CI) = 1.2–1.26, P = 1.37 × 10–61), BP (OR = 1.15, 95% CI = 1.07–1.23, P = 5.11 × 10–5), SB-Cohort-2019 (OR = 1.17, 95% CI = 1.07–1.27, P = 2.30 × 10–4), SB-Cohort-2019 in depressed patients (OR = 1.34, 95% CI = 1.16–1.54, P = 5.97 × 10–5), and SB-Cohort-2020 (OR = 1.24, 95% CI = 1.18–1.3, P = 1.47 × 10–18). Genetically proxied liability to RLS did not significantly influence the risk of any of the outcomes (all corrected P > 0.05). Results were replicated for insomnia with MDD and SB in Mass General Brigham Biobank and were consistent in multiple lines of sensitivity analyses. In conclusion, human genetic evidence supports for the first time a potentially independent and causal effect of insomnia on SB and encourages further clinical investigation of treatment of insomnia for prevention or treatment of SB.

The growing availability, legality, and use of marijuana products in the USA has contributed to increased patient and clinician interest in the treatment of sleep disorders, especially insomnia and restless legs. What should clinicians know about these drugs and what should they tell patients that inquire about using them? Increasing numbers of studies are being published revealing clear subjective improvement of sleep-onset latency, subjective improvement of sleep disruptions, and subjective improvement of restless legs symptoms. However, objective findings are most often mixed, with some studies demonstrating improvement of sleep characteristics, and some demonstrating worsening. There is a trend for improvement in sleep with short-term use of marijuana products and a longer-term attenuation of effect, or possibly worsening. Evidence for their effectiveness in these disorders is robust from subjective patient reports but limited or mixed in objective measures. Discussions with patients should be individualized and risks and benefits weighed. Future large, randomized, placebo-controlled studies are needed to help clarify the discrepancy between subjective and objective measures.

Restless legs syndrome (RLS) has a high prevalence in the elderly and can impact sleep quality and sleep quantity, reduce quality of life (QoL), and increase the risk of falls during episodes of night-time ambulation. In patients unable to verbalize their sensory symptoms, certain behavioral cues may help with the diagnosis. A state of brain iron deficiency could play a central role in the pathophysiology of RLS and be upstream to a series of dysfunctions that are not limited to the dopaminergic system. Management should initially emphasize lifestyle modifications and reduction of all possible iatrogenic contributors while maintaining a state of normal–high peripheral iron stores. Oral iron, in patients with ferritin levels

Restless legs syndrome (RLS) is a sensorimotor neurologic disorder characterized by an unpleasant urge to move the legs, often accompanied by leg dysesthesias. Symptoms predominate in the evening or at night and often cause significant distress and disruption of sleep. Several non-opioid classes of drugs provide initial relief from the symptoms of RLS. Among these, however, the efficacy of dopamine agonists can wane over time or even paradoxically 'augment' the severity of symptoms during the course of long-term treatment. Opioids can alleviate RLS symptoms, even in patients who have become refractory to, or do not tolerate, other drugs. In a carefully selected group of patients with severe RLS that has not been effectively managed with other therapies, opioids may be an appropriate treatment.

Restless legs syndrome (RLS) is a common, frequently chronic, sensorimotor neurological disorder characterized by nocturnal leg dysesthesias and an irresistible urge to move the legs, usually resulting in sleep disturbance. Dopaminergic agonists, alpha-2-delta calcium-channel ligands, and opioids have all demonstrated efficacy to relieve symptoms of RLS and improve sleep. However, long-term treatment with dopamine agonists (the most commonly prescribed agents) is often characterized by worsening symptoms and loss of efficacy. A more worrisome complication of dopaminergic agents is augmentation, an iatrogenic worsening of RLS symptoms that can produce progressively more severe symptoms resulting in around-the-clock restlessness and near sleeplessness. Recent research has yielded consensus regarding a precise definition of augmentation and has contributed to improved knowledge regarding strategies for preventing this complication. When RLS symptoms worsen during the course of treatment, the clinician must consider the myriad of environmental, medical, pharmacologic, and psychiatric factors that can exacerbate RLS. In the absence of fully developed, evidence-based guidelines there remains uncertainty regarding the optimal management strategy if augmentation develops. However, we discuss several key principles based on the available published data and the authors' clinical experience. We also explore the recent increasing interest in alternative initial treatment strategies that avoid dopamine agonists and their associated complications altogether.

Sleep complaints are commonly encountered in psychiatric clinics. Underlying medical disorders or sleep disorders need to be identified and treated to optimize treatment of the mental illness. Excessive daytime sleepiness, which is the main symptom of obstructive sleep apnea (OSA), overlaps with those of many severe mental illnesses. Medication side effects or the disorder itself maybe account for daytime sleepiness but comorbid OSA is a possibility that should not be overlooked. The diagnosis of OSA is straightforward but treatment compliance is problematic in psychiatric patients. This article summarizes studies concerning comorbid OSA in patients with severe mental illness and includes suggestions for future investigations.

Insomnia is closely related to major depressive disorder (MDD) both cross-sectionally and longitudinally, and as such, offers potential opportunities to refine our understanding of the neurobiology of both sleep and mood disorders. Clinical and basic science data suggest a role for reduced γ-aminobutyric acid (GABA) in both MDD and primary insomnia (PI). Here, we have utilized single-voxel proton magnetic spectroscopy (1H-MRS) at 4 Tesla to examine GABA relative to total creatine (GABA/Cr) in the occipital cortex (OC), anterior cingulate cortex (ACC), and thalamus in 20 non-medicated adults with PI (12 women) and 20 age- and sex-matched healthy sleeper comparison subjects. PI subjects had significantly lower GABA/Cr in the OC (p=0.0005) and ACC (p=0.03) compared with healthy sleepers. There was no significant difference in thalamic GABA/Cr between groups. After correction for multiple comparisons, GABA/Cr did not correlate significantly with insomnia severity measures among PI subjects. This study is the first to demonstrate regional reductions of GABA in PI in the OC and ACC. Reductions in GABA in similar brain regions in MDD using 1H-MRS suggest a common reduction in cortical GABA among PI and mood disorders.

Chronic insomnia is one of the most prevalent psychiatric disorders and has a significant impact on individual's health. However, the pathophysiology of the disorder is poorly understood. The current review focuses on neuroimaging findings in insomnia. In summary, the current data suggest the following: (1) insomnia is characterized by corticolimbic overactivity during sleep and wakefulness that interferes with sleep initiation and/or maintenance; (2) insomnia patients' daytime performance is associated with a hypoactivation of task-related areas; (3) neurochemically, insomnia patients are probably characterized by reduced cortical GABA levels; (4) insomnia may be associated with abnormal brain morphometry in the frontal cortex, hippocampus and/or anterior cingulate cortex. Future investigations should include larger sample sizes or longitudinal within-subject comparisons. Other possible methodological improvements are discussed.