Psychosomatic illness used to have a negative connotation, the idea being that symptoms that seem to be “all in your head” are not indicators of a real condition. But while psychosomatic symptoms may undeniably occur in reaction to stress or anxiety, the mind-body connection is very real and there are known factors that influence both. Chronic illnesses in particular are associated with an increased risk of depression and anxiety, and research indicates that schizophrenia is characterized by systemic inflammation and disturbances in metabolism.

Here we look at a few disorders that cross the line between the somatic and the psychiatric.


Rheumatoid Arthritis Risk of Depression and Anxiety

Rheumatoid arthritis (RA) is a chronic inflammatory arthritis with both musculoskeletal and systemic features. RA primarily targets the synovial membrane, cartilage, and bone, causing damage to the joints. Systemically, RA inflammation affects other tissues and organs and is associated with progressive disability and early death.

People with RA generally experience several physical and psychological comorbidities, and it is increasingly recognized that depression and anxiety are associated with high disease activity, worse disease outcomes, and decreased quality of life.1 Several cytokines are active in the joints of individuals with RA, causing inflammation and articular damage. Interleukin (IL)-1 and the cytokines of tumor necrosis factor (TNF)-α, IL-6, and IL-18 are primarily involved.

“Clinicians should be alert to neuro-psychiatric comorbidity in RA from the earliest stages of the disease when the prevalence and levels of depression appear to be highest,” said George Fragoulis, of the Institute of Infection, Immunity, and Inflammation at the University of Glasgow, United Kingdom. “Perhaps more intense screening and treatment for psychiatric comorbidities, especially in such patients as those with high C-reactive protein (CRP) levels or high Health Assessment Questionnaire (HAQ) scores can improve outcomes,” he explained in a 2020 paper.1 (Read more about this approach in our report on putting mental health on par with physical health assessments.)

Depression is also a frequently observed complication in patients with later-stage rheumatoid arthritis. While the two conditions may aggravate each other via unknown mechanisms, depression is thought to be strongly associated with systemic inflammation, and particularly with dysregulation of the cytokine network. There may be common therapeutic targets for both RA and depression treatment. In addition, RA is a chronic disease that is potentially devastating for a patient’s quality of life and may result in the development of psychiatric disorders.

See also, inflammatory biomarkers and depression treatment.

Psychological factors may be another key network responsible for depression and other mood disorders in patients with rheumatoid arthritis.2 Depressive symptoms, impaired sleep, and fatigue are common in women with RA. Poor sleep is associated with greater frequency and severity of depressive symptoms in these individuals, suggesting that screening for sleep and mood problems may be relevant in patient care.3

Mental Health and Gastrointestinal Disorders: IBS and Celiac Disease

The occurrence of psychiatric symptoms in patients diagnosed with celiac disease has been known for a long time and is increasingly reported. While the relationship between celiac disease and mental health is not fully understood, a 2020 meta-analysis showed a significantly increased risk for autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), depression, anxiety, and eating disorders among patients with celiac disease.4 (See also, a European effort to study ADHD and cardiometabolic conditions)

Psychiatric disorders and functional gastrointestinal (GI) disorders co-occur at high rates, although the mechanisms underlying these associations remain unclear. Irritable bowel syndrome (IBS) – the most common functional GI disorder – affects approximately 10% of individuals worldwide, although prevalence varies among countries and estimates vary according to the diagnostic criteria used.5 Looking at results of various published controlled trials and meta-analyses, Carra Simpson, PhD, at the University of Melbourne, Australia, estimates that approximately 84% of patients with IBS also have a depressive disorder and 44% an anxiety disorder. In turn, 45% of patients with anxiety and 30% of patients with a depressive disorder develop IBS.6

Micro-organisms in the gut have emerged as a critical component of endocrine, immune, and nervous system functioning, and research has evolved to look at the microbiome for clearer information on the etiology of IBS, anxiety, and depression. A new project, called the Bugs and Brains Study, is underway in Australia to investigate the complex relationships between anxiety, depression, and IBS.6 Led by Dr. Simpson, researchers at the University of Melbourne are comparing gut and oral microbiota in biological samples from women with anxiety/depression and/or IBS relative to controls, and investigating the underlying physiological, endocrine, and immune factors involved. They will also look at these conditions’ relationships with diet and psychosocial factors.

A second part of the Bugs and Brains Study will investigate such associations in a larger sample by questionnaire only, collecting information on mental health, GI health, oral health, diet, substance use, and psychosocial factors such as early life adversity, stress, and emotion regulation.6  (See also, the microbiome and opioid dependence on our sister site, PPM.)

Because of the high prevalence of psychiatric comorbidities such as anxiety and depression in people with IBS, experts recommend proper screening for these disorders in GI clinics. Psychological factors can be important moderators of symptom severity, symptom persistence, patients’ willingness to seek treatment, and their response to treatment. A patient’s recognition and treatment approach can significantly improve quality of life and overall outcomes.7

See also, a personal story on anxiety and conversion disorder (also known as somatic syndrome disorder and functional neurological disorder) that disrupted a teen girl’s life for two-plus years.

Metabolic and Cardiovascular Disease Risks in Psychotic Disorders, Schizophrenia

People with psychotic disorders show abnormalities in several organ systems in addition to the central nervous system (CNS), contributing to mortality 15 to 20 years earlier than those in the general population. More than 60% of these premature deaths are related to non-CNS, mostly cardiovascular causes.8

Schizophrenia specifically is associated with cognitive dysfunction as well as cardiovascular risk factors, including metabolic syndrome and its constituents. In a systematic review and meta-analysis of 27 studies, significantly greater global cognitive deficits were present in patients with schizophrenia who had diabetes, metabolic syndrome, or hypertension.9

In those with chronic psychotic disorders, a complex interaction exists between lifestyle factors, antipsychotic side effects, and lower-quality healthcare that contributes to higher cardio-metabolic risk. Research shows these individuals have increased levels of obesity (50%), metabolic syndrome (30%), glucose intolerance (25%) and type 2 diabetes (10%), together with high levels of smoking, poor diet, and low physical activity.10

In a study to determine whether targeted improvement strategies, such as regular monitoring and educational interventions, would improve some of these parameters, researchers found that some measures improved, but monitoring remained suboptimal.10 According to lead investigator John R. Kelly, MD, of Tallaght University Hospital in Dublin, Ireland, “Improving cardiometabolic health across the psychotic disorder spectrum requires ongoing awareness-raising and promotion of physical health among [clinicians] and patients, the availability of effective physical health interventions, and enhanced collaboration between primary and secondary care, all facilitated by standardized systems and enhanced utilization of IT platforms.”

Severe Mental Illness and Cardiovascular Disease

A large scale meta-analysis of the prevalence and incidence of cardiovascular disease (CVD) in people with severe mental illness (SMI) – defined as schizophrenia, bipolar disorder, and major depressive disorder (MDD) – established that the pooled CVD prevalence in SMI patients with a mean age of 50 years was 10%.8 Patients had significantly higher odds of having at least one comorbid CVD. Longitudinal analysis showed a 3.6% incidence rate of CVD during a median of 8.4 years of follow-up. Patients with SMI showed a 53% higher risk for having a CVD, a 78% higher risk for developing CVD, and an 85% higher risk of death from CVD compared to the regionally matched general population.8

Christoph Correll, MD, a psychiatry researcher at Albert Einstein College of Medicine in New York City, and colleagues identified several important moderators of increased cardiometabolic risk, including antipsychotic use, elevated BMI, and elevated baseline CVD. Based on these results, they advise that psychiatrists:

  • Only prescribe antipsychotic medications, particularly for nonpsychotic conditions, when other treatment options with lower CVD risk potential have been sufficiently tried
  • Choose the lowest-risk antipsychotic agents first when selecting a medication
  • Screen for and manage emerging and existing CVDs
  • Screen for and manage risk factors, including weight gain, body mass index, and other components of metabolic syndrome.8

Correll’s team also noted in their paper that, although their data show an increased risk of CVD with antipsychotic medication, the improvements seen in psychotic symptom control and function with medication have positive effects on general health and mortality. Therefore, when developing a treatment program, clinicians are encouraged to weigh the benefits of improved psychiatric status with antipsychotic agents against their potential for elevated cardiometabolic risk.8

The pathophysiology underlying the association between SMI and CVD risk is complex. The conditions share certain pathophysiological features, including hypothalamic-pituitary-adrenal and mitochondrial dysfunction, peripheral immune function, neuro-inflammation, oxidative and nitrosative stress, as well as genetic links and epigenetic interactions.11 Newly published research has pointed to such early-life causative factors as the compromised integrity of the placental barrier, which contributes to alterations in the infant’s immune profile and the development of low-grade inflammation, as well as the stressful effects of adverse childhood experiences.12

Persistently high fasting insulin levels during childhood have been associated with an increased risk of developing a psychotic disorder.13 In a British cohort study of 14,975 individuals, high fasting insulin levels were associated with a psychosis at-risk mental state and psychotic disorder, but not depression. Conversely, a puberty-onset major increase in BMI was associated with depression, but not psychosis.

These findings suggest that “Changes in insulin sensitivity and adiposity starting from childhood may have disorder-specific associations with psychosis and depression and represent targets for prevention and treatment of cardiometabolic disorders in people with psychosis and depression,” wrote Benjamin I. Perry, MRCPsych, of the Cambridge School of Clinical Medicine in the United Kingdom.13

Physical Health and Secondary Mental Health Effects

Psychosis as a Multisystem Disorder

Poor physical health – including some chronic pain conditions – has traditionally been blamed on the secondary effects of mental illness itself or its treatment, either because patients’ negative symptoms keep them from following a healthy lifestyle, or because they are experiencing side effects from taking a second-generation antipsychotic medication. But more recent studies reviewed by clinical research fellow Toby Pillinger and his group at King’s College in London have shown that first-episode psychosis patients already have dysfunctions in their cardiometabolic, immune, and hypothalamic-pituitary-adrenal (HPA) systems. Dr. Pillinger and his team sought to uncover some of the factors underlying these associations.14

They conducted a systematic meta-review of both CNS and non-CNS dysfunction in first-episode psychosis in 165 case-control studies comprising a total of 13,440 individuals. Those with first-episode psychosis were found to have significant alterations in immune parameters, cardiometabolic parameters, HPA parameters, brain structure, neurophysiology, and neurochemistry, compared with healthy controls. These findings also indicated that the non-CNS alterations are similar in magnitude to CNS changes.14

Dr. Pillinger’s team concluded that the evidence suggests that dysfunction across multiple organ systems is present early in psychosis – but further research is needed to elucidate whether non-CNS dysfunction is a cause or a consequence of psychosis, as well as whether psychosis could be defined as a multisystem disorder.14

Current Mental Health Screening Tools and Professional Takeaways

Clay Jackson, MD, DipTh, clinical assistant professor of family medicine and psychiatry at the University of Tennessee College of Medicine in Memphis, and former president of the Academy of Integrative Pain Management said that despite the availability of standard mental health screening tools – such as the PHQ2 for common psychiatric disorders and the PHQ9 for depression – clinicians need to be shown that these tools’ use will make a difference in patient care before they overcome their therapeutic nihilism.

“What is lacking from the clinician and payer standpoint,” said Dr. Jackson, “is an examination of a history of early childhood trauma, and the connection between that and later disease. There is a link between early childhood events and later disease and syndrome clusters [see also, Dr. Jackson’s prior report on childhood trauma and adult-onset pain on our sister clinical site PPM]. This complex interplay between the genome, epigenetics, and patients’ actions extends across the life cycle,” he said.

For example, he added, “Middle-aged patients with metabolic syndrome feel they have no control over their disease. Diabetes control is difficult, and patients get depressed. If you can show them that an anti-inflammatory diet, mental health counseling, and online resources such as meditation apps can be helpful, you have an opportunity to extend your reach beyond the episodic, brick-and-mortar encounter into a long-term relationship,” Dr. Jackson concluded.

Editor’s Note: More from Dr. Jackson and a panel of experts on the state of mental health assessments in the United States – and what’s missing – in our special report. Plus, pain psychologist Robert Twillman, PhD, talks about assessment challenges when treating individuals with co-occurring psychiatric disorders and physical conditions, and Katie Bennett, JD, examines the policies coming out of the Biden Administration to improve access to mental health services and behavioral health treatments.

Last Updated: Jun 2, 2021