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Ehrmann et al., J Sleep Disorders Ther 2013, 2:6
rnal of
Journal of Sleep Disorders & Therapy
Therapy
DOI: 10.4172/2167-0277.1000143
Jou
ISSN: 2167-0277
Review Article Open Access
Sleep-Disordered Breathing and Psychopathology: A Complex Web of
Questions and Answers
Daniel E Ehrmann1*, Bertram Pitt2 and Patricia J Deldin3,4
1
University of Michigan Medical School, Ann Arbor, MI, USA
2
University of Michigan Department of Internal Medicine, Division of Cardiology, Ann Arbor, MI, USA
3
University of Michigan Department of Psychology, Ann Arbor, MI, USA
4
University of Michigan Department of Psychiatry, Ann Arbor, MI, USA
Abstract
Sleep-disordered breathing is common but under-diagnosed. This is concerning given the emerging empirical
relationships between severe forms of sleep-disordered breathing, such as obstructive sleep apnea syndrome,
and various forms of psychopathology including major depressive disorder, attention deficit hyperactivity disorder,
generalized anxiety disorder, schizophrenia and post-traumatic stress disorder. Inflammatory pathways may
mediate part of the relationship between sleep-disordered breathing and psychopathology, but the strength and
directionality of these processes and associations remains unknown. It may be appropriate to have a heightened
index of suspicion for SDB and psychopathology in individuals at higher baseline risk for their co-morbidity. Further
investigation in larger, longitudinal, well-controlled studies is needed to understand the relationship of SDB and
psychopathology.
Keywords: Sleep-disordered breathing; Sleep apnea; plasticity [21-24]. This may contribute to the various functional
Psychopathology; Major depressive disorder and structural abnormalities (e.g., in the frontal cortex,
amygdala, basal ganglia, hippocampus, thalamus, cerebellum
Introduction and cerebral ventricles) observed in many patients with severe
Sleep Disordered Breathing (SDB) characterizes a broad SDB [25-27].
range of disorders described by abnormalities in respiratory Thus, there exists a pathway by which the neurohumoral
pattern and intake during sleep [1]. These range from snoring activation secondary to severe SDB may potentiate the impact
to Upper-Airway Resistance Syndrome (UARS) to its most of mental illness. In individuals with depression, for example,
common form, Obstructive Sleep Apnea Syndrome (OSAS) [1].
OSAS is associated with resistance to both pharmacological and
SDB in adults is more prevalent than many clinicians realize,
cognitive behavioral therapy [28,29]. Patients with treatment-
affecting approximately ten to seventeen percent overall [2,3]
resistant depression and Cardiovascular Disease (CVD) have a
with its most severe form-Obstructive Sleep Apnea (OSA)-
higher rate of cardiovascular events than those with less severe
present in five to ten percent [4-6]. SDB is not uncommon in
children, tends to increase with age, and may be increasing depression [30], and sleep researchers have wondered whether
in incidence secondary to our national obesity epidemic [5]. this is explained in part by the underlying inflammatory cascade
However, it remains one of the most elusive conditions to from incipient OSA that characterizes all three conditions
diagnose-as many as eighty percent of patients at risk for [21,31,32]. This is especially important considering that
OSA may escape formal diagnosis [2,7]. The prevalence and Continuous Positive Airway Pressure (CPAP) has been shown
elusiveness of SDB are especially concerning considering the to diminish the inflammatory cascade, improve symptoms of at
emerging associations between SDB and various forms of least two forms of psychopathology (MDD and ADHD), [14,33-
psychopathology [8,9]. 35] and reduce cardiovascular risk [36,37].
The SDB-Psychopathology Web Many Important Questions Remain
To date, SDB has been found to be associated with many Despite the emerging empirical associations and biochemical
forms of psychopathology, the most well-studied of which
include Major Depressive Disorder (MDD), [10-12] Attention
Deficit/Hyperactivity Disorder (ADHD), [13-15] Generalized
*Corresponding author: Daniel E Ehrmann, University of Michigan Medical
Anxiety Disorder (GAD), [16,17] schizophrenia [18,19] and School, 5124 Medical Science I (C-wing), 1301 Catherine Street, Ann Arbor,
Post-Traumatic Stress Disorder (PTSD) [20]. Additionally, Michigan, 48109-5611, USA, Tel: (248) 330-6924; Fax: (734) 615-0573; E-mail:
theoretical evidence exists that may link SDB with worsened
mood, memory and cognition. For example, the downfield Received August 12, 2013; Accepted October 01, 2013; Published October 17,
sequalae of intermittent hypoxia and hypercapnia secondary to 2013
severe SDB (e.g., OSA) is associated with sympathetic activation Citation: Ehrmann DE, Pitt B, Deldin PJ (2013) Sleep-Disordered Breathing and
and reduced vagal tone that is marked by release of pro- Psychopathology: A Complex Web of Questions and Answers. J Sleep Disorders
Ther 2: 143. doi:10.4172/2167-0277.1000143
inflammatory cytokines and catecholamines. These deleterious
mediators are known to contribute to relative cerebral Copyright: © 2013 Ehrmann DE, et al. This is an open-access article distributed
under the terms of the Creative Commons Attribution License, which permits
under perfusion, neuronal oxidative stress, neurotransmitter unrestricted use, distribution, and reproduction in any medium, provided the
imbalance (e.g., serotonin, glutamate), and decreased synaptic original author and source are credited.
J Sleep Disorders Ther
ISSN: 2167-0277 JSDT, an open access journal Volume 2 • Issue 6 • 1000143
S lee r
s&
Ehrmann et al., J Sleep Disorders Ther 2013, 2:6
rnal of
Journal of Sleep Disorders & Therapy
Therapy
DOI: 10.4172/2167-0277.1000143
Jou
ISSN: 2167-0277
Review Article Open Access
Sleep-Disordered Breathing and Psychopathology: A Complex Web of
Questions and Answers
Daniel E Ehrmann1*, Bertram Pitt2 and Patricia J Deldin3,4
1
University of Michigan Medical School, Ann Arbor, MI, USA
2
University of Michigan Department of Internal Medicine, Division of Cardiology, Ann Arbor, MI, USA
3
University of Michigan Department of Psychology, Ann Arbor, MI, USA
4
University of Michigan Department of Psychiatry, Ann Arbor, MI, USA
Abstract
Sleep-disordered breathing is common but under-diagnosed. This is concerning given the emerging empirical
relationships between severe forms of sleep-disordered breathing, such as obstructive sleep apnea syndrome,
and various forms of psychopathology including major depressive disorder, attention deficit hyperactivity disorder,
generalized anxiety disorder, schizophrenia and post-traumatic stress disorder. Inflammatory pathways may
mediate part of the relationship between sleep-disordered breathing and psychopathology, but the strength and
directionality of these processes and associations remains unknown. It may be appropriate to have a heightened
index of suspicion for SDB and psychopathology in individuals at higher baseline risk for their co-morbidity. Further
investigation in larger, longitudinal, well-controlled studies is needed to understand the relationship of SDB and
psychopathology.
Keywords: Sleep-disordered breathing; Sleep apnea; plasticity [21-24]. This may contribute to the various functional
Psychopathology; Major depressive disorder and structural abnormalities (e.g., in the frontal cortex,
amygdala, basal ganglia, hippocampus, thalamus, cerebellum
Introduction and cerebral ventricles) observed in many patients with severe
Sleep Disordered Breathing (SDB) characterizes a broad SDB [25-27].
range of disorders described by abnormalities in respiratory Thus, there exists a pathway by which the neurohumoral
pattern and intake during sleep [1]. These range from snoring activation secondary to severe SDB may potentiate the impact
to Upper-Airway Resistance Syndrome (UARS) to its most of mental illness. In individuals with depression, for example,
common form, Obstructive Sleep Apnea Syndrome (OSAS) [1].
OSAS is associated with resistance to both pharmacological and
SDB in adults is more prevalent than many clinicians realize,
cognitive behavioral therapy [28,29]. Patients with treatment-
affecting approximately ten to seventeen percent overall [2,3]
resistant depression and Cardiovascular Disease (CVD) have a
with its most severe form-Obstructive Sleep Apnea (OSA)-
higher rate of cardiovascular events than those with less severe
present in five to ten percent [4-6]. SDB is not uncommon in
children, tends to increase with age, and may be increasing depression [30], and sleep researchers have wondered whether
in incidence secondary to our national obesity epidemic [5]. this is explained in part by the underlying inflammatory cascade
However, it remains one of the most elusive conditions to from incipient OSA that characterizes all three conditions
diagnose-as many as eighty percent of patients at risk for [21,31,32]. This is especially important considering that
OSA may escape formal diagnosis [2,7]. The prevalence and Continuous Positive Airway Pressure (CPAP) has been shown
elusiveness of SDB are especially concerning considering the to diminish the inflammatory cascade, improve symptoms of at
emerging associations between SDB and various forms of least two forms of psychopathology (MDD and ADHD), [14,33-
psychopathology [8,9]. 35] and reduce cardiovascular risk [36,37].
The SDB-Psychopathology Web Many Important Questions Remain
To date, SDB has been found to be associated with many Despite the emerging empirical associations and biochemical
forms of psychopathology, the most well-studied of which
include Major Depressive Disorder (MDD), [10-12] Attention
Deficit/Hyperactivity Disorder (ADHD), [13-15] Generalized
*Corresponding author: Daniel E Ehrmann, University of Michigan Medical
Anxiety Disorder (GAD), [16,17] schizophrenia [18,19] and School, 5124 Medical Science I (C-wing), 1301 Catherine Street, Ann Arbor,
Post-Traumatic Stress Disorder (PTSD) [20]. Additionally, Michigan, 48109-5611, USA, Tel: (248) 330-6924; Fax: (734) 615-0573; E-mail:
theoretical evidence exists that may link SDB with worsened
mood, memory and cognition. For example, the downfield Received August 12, 2013; Accepted October 01, 2013; Published October 17,
sequalae of intermittent hypoxia and hypercapnia secondary to 2013
severe SDB (e.g., OSA) is associated with sympathetic activation Citation: Ehrmann DE, Pitt B, Deldin PJ (2013) Sleep-Disordered Breathing and
and reduced vagal tone that is marked by release of pro- Psychopathology: A Complex Web of Questions and Answers. J Sleep Disorders
Ther 2: 143. doi:10.4172/2167-0277.1000143
inflammatory cytokines and catecholamines. These deleterious
mediators are known to contribute to relative cerebral Copyright: © 2013 Ehrmann DE, et al. This is an open-access article distributed
under the terms of the Creative Commons Attribution License, which permits
under perfusion, neuronal oxidative stress, neurotransmitter unrestricted use, distribution, and reproduction in any medium, provided the
imbalance (e.g., serotonin, glutamate), and decreased synaptic original author and source are credited.
J Sleep Disorders Ther
ISSN: 2167-0277 JSDT, an open access journal Volume 2 • Issue 6 • 1000143
