Background
Mental illness is one of the most pressing contemporary problems, with impact on health, social and economic issues. Despite significant research efforts, common mental disorders within the general population remain a major concern, with reports as high as 28.8% for anxiety disorders, 20.8% for mood disorders, and 14.6% for substance use disorders [
1], as well as rates of up to 40% for subjects with a mental disorder to meet criteria for another class of lifetime disorder [
2].
In addition to high comorbidity between mental disorders, there is also vast evidence that people with common mental health conditions are at higher risk of developing physical illness, and conversely people with a diagnosis of physical illness are at higher risk of developing mental health conditions [
3]. For instance, robust associations between immunological/ inflammatory conditions and mood disorders [
4] have been identified, with depressed patients being 60% more likely to develop diabetes than their non-depressed counterparts and prevalence rates of diabetes as high as three times greater in subjects with bipolar disorder [
3]. Further, in patients with schizophrenia, cardiovascular disease is the most common cause of death [
5]. Of note, while highly relevant, the comorbidity between mental health and physical conditions is often neglected [
6]. Here we argue better understanding this comorbidity may lead to improved prognosis and outcomes. The aim of the current study was therefore to delve into the relationship between mental and physical health conditions, as to highlight features important in explaining the development of this comorbidity.
In recent years it has been suggested that some symptoms of particular diagnoses, but not all, may account for the comorbidity patterns between diagnoses, indicating that symptoms may have a unique role and may not be interchangeable [
7]. This line of reasoning, now known as the
network framework [
8] has been proposed as an innovative tool in the study of psychopathology, and in the past decade it has grown prominent in the fields of psychiatry and clinical psychology [
9]. Within this framework, the focus shifts from the diagnostic level to the symptom level, with the aim to highlight the unique role of symptoms, and their potential causal associations. Network structures may therefore be useful tools to study both within-diagnoses and between-diagnoses symptom associations.
Further, the network approach suggests that the boundaries between mental and physical disorders are porous [
10], as physical symptoms can cause psychopathological symptoms (e.g., pain - > fatigue - > depressed mood) and vice versa (e.g., depressed mood - > alcohol use - > liver damage). If so, it is crucial to chart the pathways by which these influence each other, as to ultimately reach better treatment targets. The current research aims to highlight features that may account for comorbidity between diagnoses and provide an encompassing view of unique associations between psychopathological conditions and chronic illness and functioning. To this end, we aimed to constructed a large network structure, encompassing a multitude of symptoms and other health-related dimensions, ranging from general psychopathology, to psychosis, alcohol use, chronic physical conditions and functioning and health-related quality of life (HRQoL). To our knowledge, this is the first and only network-based study encompassing such as multitude of health-related domains, as well as the only existing network study concerned with the comorbidity between mental and physical health conditions.
Discussion
The current study used a network approach in an aim to uncover associations, at a subclinical level, between a wide array of psychopathological conditions, chronic illness and functioning. To our knowledge, this is the first study to focus on such a multitude of complex relations between different physical and health-related domains. Overall, we identified what we have labeled a Cartesian graph: a network graph split into two visible domains: a (mainly) psychopathological domain (more generally referred to as the mental health domain), and a (mainly) functioning and chronic conditions domain (more generally referred to as the physical health domain). The borders between these two domains are fuzzy and bridged by various cross-domain associations.
To date, there is wide evidence supporting the comorbidity between physical conditions and mental disorders [
3,
4], with a majority of findings indicating mood and anxiety disorders as the main comorbid feature [
26‐
29]. Although the current study identified few links between specific anxiety- and depression-related symptoms and chronic conditions, most chronic conditions were associated with items related to functioning, which were in turn associated to reports of anxiety/ depression–the main bridging item between the domains. Notably, the anxiety/ depression item, as well as the remaining functioning items were designed to measure the presence of
current symptomatology, while the rest of psychopathological items were designed to measure
lifetime presence of symptomatology. Taken together and in line with high rates of relapse for depression [
30] and generalized anxiety disorders [
31,
32], these findings suggest that overall lifetime symptomatology may predict current symptomatology (i.e., subjects with lifetime symptoms may report more current symptoms and vice versa), and current symptomatology may in turn be linked to current levels of functioning. Further, our results indicate that functioning plays a unique role and is a crucial bridging component in linking chronic conditions to psychopathology. It may thus be that when chronic conditions are associated with a decrease in functioning and thus low HRQoL reports, psychopathological symptoms may be triggered. Similarly, chronic psychopathology affecting daily-life functioning may lead to a rise in other physical chronic conditions. Previous research indeed identified that better functional status and fewer depressive symptoms were significantly associated with a higher quality of life in adults with chronic conditions [
33]. Centrality analyses further support these findings, with functioning and depression items being most central in the current network structure. In addition, in line with outcomes showing high comorbidity between physical conditions and mental conditions [
3,
4], we found that self-reports of physical and mental well-being were strongly linked together, indicating that subjects reporting poorer mental health are more likely to also report poorer physical health and vice versa.
Other between-domain links included associations between asthma and depression, social phobia, and ODD. Previous research identified that children diagnosed with and taking medication for asthma were more likely to endorse common behavioral problems [
34], while lifetime and current asthma diagnosis were associated with a range of mental disorders, including social phobia and affective disorders [
35]. We further found hypertension and gambling to be linked, even when controlling for alcohol use and smoking, supporting findings on the detrimental effect of gambling on physical health [
36]. Further, within the psychopathology domain, smoking, gambling, and alcohol were well-clustered items, the comorbidity between the addictions being well-documented [
37‐
39]. Smoking was further associated with psychosis, in line with evidence that smoking is common in psychotic disorders [
40]. In addition, interestingly, the psychosis item was the only psychopathological item that fell in between the two domains of the network, being connected to psychopathology, but also to the chronic conditions through its association with migraine headaches. Side-effects of antipsychotic medication can include headaches [
41,
42], but some evidence suggests severe forms of migraine–such as migraine aura–can also be associated with psychotic manifestation [
43‐
45]. Psychosis and obsessions were also interrelated, indicating this association may already present at subclinical levels of psychopathology, and not only in patients [
46], or in subjects at ultra-high risk for psychosis [
47]. Finally, the obsessions item was one of the more central items in the network, being extensively associated to psychopathology. Of note, recent research showed OCD to have one of the largest treatment gaps (89.8%) in Singapore [
48], highlighting the importance of addressing symptomatology early and encouraging help-seeking behavior.
Finally, within-domain and within-cluster associations were stronger and predominantly positive, suggesting activation may spread faster within the same domain. In addition, some psychopathology symptom clusters displayed lower connectivity to others (e.g., specific phobias) than other symptom clusters (e.g., depression, anxiety, childhood disorders), indicating the latter may be more comorbid. These results align with previous research [
7] investigating the network structure of the Diagnostic and Statistical Manual for Mental Disorders (DSM) [
49]. Of note, previous research [
7] relied on a skip structure, which is problematic when constructing network structures [
50]. The current study overcame this limitation
4 and is thus the first to approximately assess the structure of a wide variety of mental disorder symptoms, overcoming an important limitation of earlier work.
The current research aimed to take a first step towards identifying important features in the development of the comorbidity between mental and physical health, by zooming into and bringing together a multitude of health-related domains. While the research is exploratory in nature and preliminary, a key finding of our research is the crucial role played by functioning in bridging chronic conditions and psychopathology. This finding indicates that when chronic conditions are associated with a decrease in functioning, psychopathological symptoms may be triggered and vice-versa. Functioning may thus be a potential key target for treatment: by tackling problems in functioning early on we may be able to circumvent problems arising in other health-related domains. Further, functioning was especially related to current complaints of anxiety and depression, which were in turn related to long-term psychopathological complains, adding to the importance of addressing functioning complaints in intervention strategies. In addition, we identified gambling to be one of the addictions that paved ways to both physical and mental health problems and psychosis to be the main psychopathological domain to fall in between the physical and mental health domains. These results indicate that approaching these conditions holistically by taking into account both physical and mental health complaints is essential, as leaving out any one component may lead to a faster activation of problems in that specific domain, ultimately leading to feedback loops and complaints in both physical and mental health domains. Alongside these main findings, we discussed within-domain and within-cluster associations, pinpointing to depression, anxiety, and childhood disorders as being more connected clusters and thus more likely to lead to activation of other disorders and therefore comorbidity.
Of note, as highlighted above, our study is exploratory in nature and preliminary. Future research is essential for expanding on our findings, by including more diverse samples (e.g., focus on a world-wide population, clinical populations, and so forth), as well as a wider array of variables concerned with chronic conditions. Here, due to the nature of data collected, we were limited to investigating only five types of common chronic conditions, as well as five functioning problems. Network studies designed specifically to investigate this comorbidity could expand on the inclusion and selection of variables, as to provide further information on this comorbidity. Alongside the replication of our results, this will enable better pinpointing of treatment targets, which may provide to be essential in reducing the comorbidity between mental and physical health. Ultimately, experimental designs built upon results from exploratory research can further lead to insights into treatment development.
In sum, we highlighted complex associations between a multitude of health-related domains. Our main findings include the identification of (1) a Cartesian graph consisting of a mental and a physical health domain, (2) functioning playing a crucial role in bridging chronic conditions and psychopathology, and (3) several within- and between-domain associations informative for potential pathways to comorbidity.
Limitations
Our results should be considered in light of several limitations. First, the current study was based on cross-sectional data which precluded strong inferences on causal direction, and therefore any conclusions regarding direction of causality are tentative. Second, the WMH-CIDI [
13] interview encompasses self-report statements, and may be prone to bias due to social desirability or under-reporting of symptomatology. Further, the current study focused on complete data cases and did not include severity of items in the analyses. Clinical samples may display different patterns of associations and current results were discussed in light of subclinical level of psychopathology. Finally, the study was carried out in a very specific population of residents of Singapore, and therefore the extent to which they generalize to other cultures is not yet known.
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