282 Current Respiratory Medicine Reviews, 2007, 3, 282-285 1573-398X/07 $50.00+.00 © 2007 Bentham Science Publishers Ltd. Depression in Sleep Related Breathing Disorder Shyam Subramanian *,1 , Mary Rose 1 and Salim Surani 2 1 Baylor College of Medicine, Houston, Texas, USA 2 Texas A&M University, Texas, USA Abstract: Sleep deprivation and sleep disruption have long been associated with mood disorders, both as a cause as well as an effect. Sleep-disordered breathing results in significant and persistent sleep disruption, which in turn leads to signifi- cant neurocognitive deficits [1,2] and major depression [3-6]. Various pathophysiologic mechanisms may play a role in modulating mood changes in these patients. Treatment for sleep-disordered breathing often improves mood [4, 7], though the data may suggest a placebo response [8]. Patients with sleep-disordered breathing should be carefully screened for mood disorders, and patients with major depression should be screened for possible underlying sleep-disordered breath- ing. Keywords: Depression in OSA, sleep and depression, OSA and mood disorder, OSA and sleep disruption. INTRODUCTION Sleep is an essential restorative physiologic process. Dis- rupted sleep leads to perturbations in health and has physical as well as psychosocial consequences. Obstructive sleep ap- nea syndrome (OSAS) is a commonly under-recognized chronic disease; the Wisconsin Sleep Cohort Study of adults between 40-59 years found that 24% of males and 9% of females are afflicted by OSA as defined by an AHI of 5 events/hour of sleep [9]. Epidemiological studies indicate that OSA is more prevalent than asthma and as prevalent as diabetes mellitus. Depression is also a common illness that has an estimated lifetime prevalence rate of 20% in adults, and which often goes unrecognized or untreated. Research over the past decade has thrown new light into how these two conditions inter-relate. PATHOPHYSIOLOGY Obstructive sleep apnea is characterized by recurrent episodes of upper airway narrowing or closure which lead to limitation of airflow. This causes both an increase in respira- tory effort as well as possible falls in oxygen saturation in the blood, both of which lead to sleep fragmentation and arousal. This in turn restricts the amount of restful slow wave and REM sleep, both of which are crucial for healthy cardiopulmonary functioning. These patients hence wake up tired with significant daytime sleepiness and fatigue. The degree and severity of sleep disruption and daytime sleepiness have both been well-correlated with depression. For those whose apnea results in desaturation, low oxygen levels can directly lead to changes in the brain white matter that may in turn lead to a host of neurocognitive impair- ments, including depression. Serotonin is a crucial neurotransmitter to the pathogene- sis of depression. Interestingly, serotonin delivery has been shown to be reduced to upper airway dilator motor neurons in sleep, and this contributes, at least in part, to sleep-related *Address correspondence to this author at the Baylor College of Medicine, 1709 Dryden St., St. 950, Houston, TX 77030, USA; E-mail: ssubrama@bcm.edu reductions in dilator muscle activity and upper airway obstruc- tion. Serotonin reuptake inhibitors have now become the mainstay of the treatment of depression, and while their direct therapeutic benefit to improving sleep apnea is not established, trials are underway to develop newer serotonin modulators to explore the possibility of developing a pharmacological strat- egy for treating sleep apnea. Obstructive sleep apnea is associ- ated with proinflammatory cytokines, including tumor necro- sis factor (TNF)-; interleukin (IL)-1, IL-6, and IL-8 [10, 11]; and C-reactive protein (CRP) [12], all of which may play a role in modulating major depression, and the neuroendocrine changes associated with depression, including perturbations to the hypothalamo-pituitary axis (HPA) (Fig. 1). CLINICAL OVERLAP Patients with OSAS frequently report feeling tired, fa- tigued, sleepy, and poorly motivated. Such symptoms often affect the individual’s job performance, undermine family relationships, and often ultimately limit overall quality of life. Patients with OSAS may have difficulty concentrating, difficulty with memory, may become irritable or withdrawn, and may find themselves losing interest in, or pleasure from activities that should be an integral part of their lives [13]. Loss of libido and sexual dysfunction is also seen commonly in these patients [14, 15]. These symptoms bear striking similarity to some of those ascribed to depression, and all contribute as symptoms in major depression Diagnostic and Statistical Manual of Mental Disorders IV [16], IV criteria. In fact, depressive symptoms in one study were shown to explain ten times the variance in fatigue in OSA patients as did OSA severity itself REF. Moreover, OSAS is associated with significant co-morbidity including cardiovascular, as well as metabolic disease states, and these in turn are inde- pendently associated with depression as well. Also, there is a significant prevalence of secondary insomnia in patients with sleep apnea, and there is a very strong inter-relationship be- tween insomnia and major depression. CORRELATION STUDIES Cross-sectional studies using depression scales in pa- tients with OSAS have, for the most part, shown a high