Physical comorbidities in men with mood and anxiety disorders: a population-based study

For centuries, it has been hypothesised and debated that a mind-body interaction exists. Over time, an evidence base has grown to support this notion, yet an incomplete understanding prevails [1, 2]. Rates of depression and anxiety are generally higher among the physically ill than in the general population; however, results vary according to the type and severity of the chronic disease and methods of ascertainment [3, 4].

Within clinical samples, patients with depression have been found to have a significantly higher number of somatic symptoms [5] and a higher risk of chronic diseases [6–8], such as coronary heart disease [9, 10], congestive heart failure [11], stroke and dementia [12], diabetes [13, 14], gastro oesophageal reflux disease (GORD) [15], osteoarthritis and rheumatoid arthritis [16], psoriasis [17], cancer [18], neurological disorders [19], pulmonary disease [20], liver disease [21], thyroid disorders [22] and asthma [23, 24], as well as non-specific syndromes such as obesity [25], anaemia [26], renal dysfunction [27], chronic fatigue syndrome [28], chronic headaches [24], and chronic pain [29]. The strength of the association as well as the extent of the evidence varies for each medical condition.

Similarly, anxiety disxorders, have been shown to be related to several medical conditions, such as cardiovascular disease [30], cancer [18], obesity [31] and other metabolic disorders [32], irritable bowel syndrome [33], gastrointestinal problems [34], GORD [15], thyroid disorders [35], psoriasis [17] and a higher number of medical symptoms [36]. In addition, as recently reviewed by Culpepper and colleagues, migraine and chronic pain, diabetes, peptic ulcer, arthritis and pulmonary disease are also associated [2].

The co-occurrence of mood or anxiety disorders and physical illness worsens the impact of symptom burden [36], impacts disease course, links to the deteriorating patient’s health status and functioning [7, 37], affects medication response and treatment adherence [38], and increases the risk of complications [39] and even death [37]. Moreover, the comorbidity between mental and physical illness is relevant in terms of role impairment and work performance [24], as well as quality of life and health service use and costs [40].

The causal pathway between comorbid mental and physical illness is complex and remains unclear. It has been suggested that the bi-directionality of this relationship may involve several mechanisms [41, 42] including biological (for example, increased pro-inflammatory cytokines, hypothalamic-pituitary axis deregulation, autonomic nervous system dysfunction, serotonin depletion, metabolic, immune and endocrine changes) [43], psychological (for example, behavioural, psychodynamic and cognitive factors) [44] and social (for example, impaired social support, loneliness, and social disengagement) [45]. Furthermore, psychotropic medication use has been linked to a higher incidence of an array of health outcomes, including diabetes, falls and bleeding, osteoporosis, and sudden cardiac death [46–48].

Enhancing the quality of care for those with mental illness not only can improve mood and anxiety symptoms, but also physical health in patients with comorbid mental and physical illness [49]. Furthermore, treatment for these disorders may influence each other [50]. Thus, estimating the prevalence and understanding the association between mood and anxiety disorders and physical illness is important in order to make more accurate diagnoses and to provide integrated and effective treatment, with regard to syndrome reciprocal influences and medication interactions. Given these data, we aimed to describe the relationship between comorbid mental and physical illness in a large, representative sample of men residing in Australia, utilising structured clinical interviews, medical records, and clinical and self-reported data collected as part of the Geelong Osteoporosis Study (GOS) [51].

Our population-based study reports associations between mood and anxiety disorders and physical illness. Mood disorders were associated with increased risk of many of the disease groups (GORD, neurological features, such as recurrent headaches and syncope and seizures, liver disorders and pulmonary diseases in older men). Anxiety disorders presented a different profile; thyroid disorders, GORD, gastrointestinal disease, metabolic risk factors, and psoriasis were more common among individuals with anxiety disorder. Importantly, mood and anxiety disorders were both associated with high medical burden.

Our results confirm other population-based data investigating the association between mood disorder and GORD [60, 61]. In a sample of over 60,000 participants residing in Norway, those identified with depressive, anxiety and comorbid symptoms, as measured by the Hospital Anxiety and Depression Scale, had a two- to three-fold increased risk of reflux symptoms, self-reported severe symptoms of recurrent heartburn or acid regurgitation [62]. Moreover, mood disorders have also been shown consistently to be more prevalent in patients with GORD in clinical practice [15, 63].

Chronic headaches are high prevalence disorders, with as many as 46% of the adult population reporting headaches, 11% migraines and 42% tension headaches [64]. Similar to our findings and other population-based studies [65, 66], Scott et al. [24] utilising data pooled from 18 general population surveys reported those identified with either non-comorbid depression or comorbid depression and anxiety, as measured by the Composite International Diagnostic Interview, had an age and gender adjusted odds ratio of 2.5 and 4.0, respectively, for chronic headaches.

In regard to syncope and seizures, our results support Morgan et al. [67] who reported fainting, blackouts and dizziness, for which there is no adequate physical explanation, were associated with undiagnosed psychiatric disorders. Depression has also been shown to co-occur with epilepsy. Recently, the association has been viewed according to the diathesis-stress model, with depression resulting from the chronic stress associated with the threat of recurring seizures, as there is little evidence linking specific epilepsy related factors (for example, focus site) to low mood [68].

Akin to our results, Wilhelm and colleagues [69] reported an association between depression and liver pathology in a population-based survey of 10,641 adults; however, the relationship was not sustained following adjustment for demographic and behavioural confounders including drinking behaviour. Excessive alcohol consumption is known to be highly correlated with liver disease [21]; however, the association persisted following correction for alcohol in our study.

In our sample, only older men with a mood disorder were at increased risk of pulmonary disease. Although the association between asthma and mood disorder is evident across the full adult age range [23], chronic bronchitis and emphysema are more common among older people and most likely contribute to the different pattern observed for older and younger men. Furthermore, pulmonary disease can be considered in stages reflecting severity, a factor we could not explore [70].

Musculoskeletal and gastrointestinal disorders tended to be associated with mood disorders, although we speculate that the heterogeneous groupings we employed may have diluted associations in our sample population. Mood disorders and symptomology have previously been shown to be associated with low BMD and subsequent fracture, where both biological and medication related processes are thought to play a role [71]. Similarly, mood disorders have been shown to be associated with gastrointestinal disorders in both clinical and population-based samples [72–74].

In contrast to other population-based studies, we did not detect a relationship between mood disorders and thyroid disorders, metabolic risk factors, cardiovascular disease, cancer and psoriasis in this sample of men. The link between mood disorders and cardiovascular disease, thyroid disorders and metabolic risk factors, in particular, is well documented [22, 24, 30]. We hypothesize that these results may be influenced by a healthy participant bias, a common issue where study participants are required to be healthy enough to attend the research centre. Furthermore, disease grouping and data collection limited our ability to identify the degree of illness severity (that is, severe stroke, TIA and medically controlled hypertension were grouped) or time since onset of the physical condition.

As with mood disorders, GORD and gastrointestinal disorders were also associated with anxiety disorders. Anxiety has been previously considered to be a non-disease related factor that impacts negatively on quality of life associated with GORD [75] and, as previously discussed, is commonly observed within population-based samples reporting GORD symptoms [62]. Furthermore, data from the present study concur with previous studies indicating that those with anxiety disorder have higher rates of gastrointestinal disorders [34].

Psoriasis has been previously associated with anxiety disorders. Harter and colleagues [34] demonstrated that patients with a lifetime history of generalised anxiety disorder or panic disorder reported significantly higher lifetime prevalence rates for dermatological disorders, including psoriasis. Why this association is seen with anxiety disorders only in our sample population is unclear.

Thyroid disorders and metabolic risk factors have also been associated with anxiety disorders. In our study, anxiety was linked to a combination of the most common risk factors for metabolic disorders, such as hypertension, diabetes, hypercholesterolemia and obesity, which Culpepper and colleagues reported to be all likely due to a prolonged stress response in patients with untreated anxiety disorder [2]. Similarly, Simon et al. [35] reported an increased risk of thyroid disorders in patients with generalised anxiety disorder, social phobia or panic disorder and recommended screening for thyroid dysfunction in patients with anxiety disorders.

Our data suggest that both mood and anxiety disorders are associated with overall medical burden. These findings are consistent with previous studies showing both depression and anxiety to be associated with an increased number of somatic conditions [5, 76]. It is plausible that this relationship may be due to mood and anxiety disorders causing physiological changes, as well as poorer self-care and treatment adherence, which in turn increase medical burden [36]. On the other hand, an increased physical burden, causing functional impairment, may result in the development of an anxiety and/or mood disorder, which have been shown to have a negative impact on clinical outcomes [77].

A major strength of our study is that the sample population spans the full adult age range, in contrast to previous studies that have mainly focused on older patients. An age interaction was only evident when exploring the association between mood disorders and pulmonary disease; thus the relationship between mental illness and each of the physical conditions was consistent across all ages. Further strengths of the study include the measurement of mood and anxiety disorders, diagnoses were made utilising semi-structured clinical interviews (SCID-IV), a gold standard tool, and the consideration of several possible confounding factors. However, our observations must be considered with caution. Ascertaining medical conditions by a self-report checklist may be compromised by imperfect recall and response bias error. Although many of these disorders were based on self-report of a physician’s diagnosis, which have been demonstrated to generally agree with medical record data [78], where possible this was confirmed by medical records, medication use or clinical data. The cross-sectional nature of the study does not allow verification of a cause-effect relationship between mental and physical illness, longitudinal studies are needed to determine the directionality of this relationship. Finally, we were unable to make a distinction between diseases with an episodic course and those with ongoing symptoms, which may impact differently on psychological status.

Our study provides further population-based evidence supporting the link between mental and physical illness in men. Recognising the link between these illnesses is important in order to manage the development of mood and anxiety disorders in response to a medical condition, or the presence of physical pathologies due to predisposing psychiatric disorders. Integrating treatment approaches and monitoring comorbidity of mental and physical illnesses is likely to improve disease course and outcome as well as enhance patients’ functional and health status, potentially reducing healthcare utilisation.