The Multidirectional Nature of Mental Illness, Chronic Disease, & Sleep

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The cycle of sleep and wakefulness is one of the most integral and intricate functions of human life, and it involves a complex set of interactions between neural circuits, neurotransmitters, and hormones.1 Sleep is aligned with the night/day cycle of the earth, and disruption in sleep homeostasis is inherently related to an individual’s well-being, including their mental and physical health.2 Poor sleep quality is associated with a higher rate of depressive symptoms in healthy subjects, and sleep disturbances are common in mood disorders like major depression.2 A 2021 population-based study of US adults found that inadequate sleep was associated with significantly increased odds of mental distress after controlling for confounding variables.3

Dysfunctional sleep patterns may also affect chronic disease development, and vice-versa, as the relationship between sleep, mental health, and physical health is frequently multidirectional.4-7 In fact, some research indicates that patients with severe mental illness have a 10 to 20-year shorter life expectancy when compared with the general population, primarily due to physical chronic disease.8,9 However, while researchers know that sleep is a process of restoration and recovery, it is somewhat unclear whether sleep duration is affected by mental health factors consequent of chronic disease or by the pathological expression of the chronic disease itself.5

Some research suggests that low-grade inflammation may promote changes in the cellular components of the blood-brain barrier, particularly on brain endothelial cells.10 A recent study evaluated whether the interrelation of sleep, mental, and physical health can be linked to shared neurobiological mechanisms, and how much these relationships are driven by genetic factors.2 Sleep behaviors are heritable, and various genetic, metabolic, behavioral, and psychological risk factors have been suggested for the development and maintenance of poor sleep quality and sleep disorders.2 The study’s authors found a phenotypic relationship between sleep and depression, BMI, and intelligence, as well as a genetic correlation between sleep quality and quantity, BMI, and intelligence in one sample. Specifically, the findings suggest that inadequate sleep is linked with increased BMI, a risk factor for chronic diseases such as obesity, heart disease, high blood pressure, type 2 diabetes, and more. Researchers also observed neutral and positive associations between depression and unhealthy sleep behaviors, highlighting the complex relationship between sleep and mental health.2 Research continues to evolve.


Links between schizophrenia and abnormal sleep were first described in the late 19th century by the German psychiatrist Emil Kraepelin.1 Clinical levels of insomnia are reported in more than 80% of patients with schizophrenia, and sleep and circadian rhythm disruption (SCRD) is increasingly recognized as one of the most common features. Mental illness, in general, and SCRD are often considered to arise from factors such as social isolation, side effects of medication, and/or activation of the stress axis. However, recent research suggests that this explanation may be overly simplistic, as SCRD is not only common in psychoses but also has widespread effects ranging across many aspects of the neural and neuroendocrine function. Many of the pathologies caused by SCRD, including cardiovascular stress, metabolic abnormalities, elevated cortisol and adrenaline, and overall poor health, are routinely reported as co-morbid with neuropsychiatric illness but are rarely linked to the disruption of sleep.1

The emotional dimensions of chronic disease, which often manifest as depression and/or anxiety, may be precipitated or exacerbated by disturbed sleep.11,12 Findings from the first large-scale transdiagnostic study of objective measured sleep and mental health suggest a strong connection between mental illness and poor sleep quality, including waking up more often and for longer periods of time.13 The study, published in October 2021 in the journal PLOS Medicine, used accelerometry recordings, which provide a scalable way to objectively measure sleep properties in psychiatric clinical research and practice, in 89,205 patients. Sleep measures—including bedtime and wake-up time, sleep duration, number of awakenings, and variability in bedtime and sleep duration—were tested for association with schizophrenia spectrum disorders, bipolar disorder/mania, major depressive disorder, and anxiety disorders. Researchers found that sleep pattern differences were ubiquitous across diagnoses, and having any psychiatric diagnosis was significantly associated with differences in every sleep measure, except for total sleep duration.13

Of course, severe, enduring mental illnesses are considered chronic diseases in and of themselves. Additionally, mental disorders may mediate or exacerbate relationships between sleep duration and other chronic diseases.14 A large study in 2013 assessed the relationship between insufficient, frequent mental distress, obesity, and chronic disease, using data from 375,653 US adults aged 18 years and older.7 The researchers found that there were significant relationships for both frequent mental distress (an indicator of psychological distress) and obesity with each of the six chronic diseases: diabetes, high blood pressure, coronary heart disease, stroke, asthma, and arthritis.7 Consistent with data from prospective studies, this study demonstrated a highly significant relationship between insufficient sleep and frequent mental distress and between frequent mental distress and chronic disease.7 Other chronic diseases associated with sleep quality and mental health include chronic obstructive pulmonary disease6 and migraine.15

Underlying Mechanisms

Numerous factors contribute to sleep disruption, ranging from lifestyle and environmental factors to genetics or other medical conditions.16 Sleep disruption is associated with increased activity of the sympathetic nervous system and hypothalamic-pituitary-adrenal axis, metabolic effects, changes in circadian rhythms, and proinflammatory responses.16 Developing an understanding of the underlying mechanisms that contribute to and connect sleep dysregulation to mental illness and chronic disease is an ongoing area of research.

Levels of catecholamines, including norepinephrine and epinephrine, have been correlated with fragmented sleep, and chronic persistent insomnia is associated with increased secretion of cortisol, which is present throughout a 24-hour sleep-wake cycle.16 Suppression of slow wave sleep (the most restorative form of sleep) is associated with decreased insulin sensitivity, and other metabolic changes include decreased leptin and increased ghrelin that may contribute to increased appetite.16 Sleep abnormalities also lead to changes in proinflammatory cytokines such as tumor necrosis factor alpha, interleukins 1 and 6, and C-reactive protein.16 Inflammation is often a factor in chronic disease development,17 as well as some mental illnesses like depression.5 The direct mechanism by which sleep induces a low-grade inflammatory status remains unclear.

Clinical Applications & Considerations for Patients With Mental Illness

Sleep and chronic disease are closely associated with mental illness, one of the most common reasons for a patient to visit a primary care provider.8 Growing evidence suggests that lifestyle interventions, including nutrition, physical activity, and adequate sleep, are effective components for the management of mental illness to improve physical health and quality of life.8,18 Certain diets may reduce the risk of developing depression and anxiety,19 while regular exercise may improve sleep and chronic disease development.20-22 Many mind-body interventions may also help patients relax into sleep.23 However, patients with mental illnesses who are managing chronic conditions, including sleep dysfunction, might already be overwhelmed and may have a difficult time incorporating behavioral modifications into their daily routine.24

Several studies have documented patient-level barriers encountered during engagement in behavioral interventions among people with serious mental illnesses.25 In a 2019 survey, patients reported that being asked to significantly alter their lifestyle caused additional stress when they were already overwhelmed by trying to cope with mental illness symptoms. Other patients who reported depression as a barrier recognized that mood symptoms, including amotivation and anhedonia, influenced future-oriented thinking, sometimes by making it difficult to think ahead.25 What other roles might mental health symptoms play in impeding a patient’s ability to make lifestyle changes, and how can clinicians help their patients fully embrace this change?

Clinicians may want to consider a patient’s mental health factors prior to developing their plan for lifestyle change. Some points to review may include:

  • Is your patient ready to consider this change?
  • What might your patient need to give up in order to embrace change?
  • What barriers might your patient face that might discourage lifestyle change?
  • How has your patient successfully changed behavior in the past?

To initiate and maintain lifestyle changes, patients with mental illnesses and other chronic diseases need their clinicians to be empathic; to help them create a shared vision for a healthier future, particularly when depression thwarts optimism; and to address unmet mental health needs through referrals to appropriate, evidence-based treatment.25 Lifestyle goals and targets can be tailored to patients’ preferences and progress while building confidence in small steps.26 More often than not, behavioral change occurs gradually over time. Patients who are mindful of their decision-making when it comes to lifestyle change, and who are more conscious of the benefits of changing an unhealthy behavior, may find it easier to adhere to clinician-prescribed behavior modification.27

A healthcare provider can play a critical role in this process by increasing patient awareness through a collaborative approach to sharing information, education, and personal feedback. The functional medicine model was developed, in part, to do just this. Functional medicine is grounded in a mutually empowering patient/provider relationship. Specific tools—like the IFM Timeline and Matrix—help the practitioner understand the course of the patient’s life as seen through the lens of health and disease. Often, disease occurs when fundamental lifestyle factors like diet, movement, rest, and/or sleep are lacking or imbalanced in an individual’s life. IFM offers a range of tools—like the IFM Food Plan and Elimination Diet—to guide the practitioner in designing a personalized treatment plan that helps the patient achieve an optimal outcome.

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