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Personality disorders and physical comorbidities

a complex relationship

Dokucu, Mehmet E.a; Cloninger, C. Robertb

doi: 10.1097/YCO.0000000000000536

Purpose of review It is not uncommon for clinicians to label patients’ complaints as ‘psychogenic’ when they present with symptoms that are difficult to understand. This article reviews recent reports about the comorbidity of personality disorders and nonpsychiatric medical problems, which call into question the adequacy of the mind-body dichotomy in medicine.

Recent findings The strong association of any personality disorders with poor health in cross-sectional and community-based studies is now confirmed by personality disorder predicting future deterioration in longitudinal studies. Borderline personality disorder has been studied most frequently, but recent data suggest that severity of any personality disorder is associated with poor and worsening health.

Summary Personality disorder is associated with the full range of physical, mental, and social disorders. Greater attention to the common features of personality disorders, which are crucial for the self-regulation of behavior, would facilitate more effective health promotion and disease prevention across all medical specialties, thereby helping to relieve the burdens of chronic common diseases.

aDepartment of Psychiatry & Behavioral Sciences, Northwestern University Feinberg School of Medicine, Chicago, Illinois

bDepartments of Psychiatry, Psychological and Brain Sciences, and Genetics, Washington University School of Medicine, St. Louis, Missouri, USA

Correspondence to C. Robert Cloninger, Washington University School of Medicine, St. Louis, Missouri, USA. E-mail:

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Modern medicine is strongly reductionistic in its search for molecular causes of disease. It tends to focus on individual diseases, which is reinforced by the division of medicine into many specialties that sometimes neglect the coordinated interdependence of all of a person's organs for health. Such reductionism and division may have begun as a useful didactic and analytic exercise to help cultivate knowledge and expertise, but it has become reified into a description of the true nature of disease as a collection of separate disorders with specific molecular causes. More generally, the body–mind dichotomy is increasingly rejected in philosophy and ethics, but has been retained in medicine as the separation of psychiatric disorders from physical and social disorders. These artificial divisions create an illusory chasm that leads to serious difficulty in approaching our patients as a whole person, even though person-centered medicine is crucial for health promotion, disease prevention, and reduction of the personal, social, and economic burdens of common diseases, such as cardiovascular disease, cancer, chronic obstructive lung diseases, diabetes, obesity, and depression [1].

In real life, individual patients usually experience more than one disorder. This concept has been termed ‘comorbidity’, ‘polymorbidity’ and ‘multimorbidity’. These terms, their history, operational definition, and the clinical and research implications of this concept have been reviewed by North et al. [2] recently.

Emotional states can affect physical health. This so-called psychosomatic connection has been recognized throughout history starting with the ancient physicians [3].

Broadened to Somatic Symptom Disorder from its original form in Diagnostic and Statistical Manual (DSM)-5, the modern medical understanding of this inseparability is documented in the extensive studies of the disorder eponymously titled Briquet Syndrome.

The comorbidity of personality disorders and physical disorders has not been recognized to the extent that comorbidity has been recognized among mental disorders or among physical diseases. Our literature search has only identified one review article in this very journal by Frankenburg and Zanarini [4] summarizing the limited literature preceding their review. Our aim here is to update their review with the newer studies undertaken in this emerging area of study since then. We will also comment on the need and rationale for better recognition of this complex and dynamic medical phenomenon. Our focus will be on personality disorders. There is also an area of research exploring personality traits and temperament in the context of medical disorders (such as Type D personality and heart disease) including the so-termed ‘functional’ medical disorders, such as chronic fatigue syndrome, which we have excluded from this review.

Box 1

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Following their thematic review in this journal in 2006, Frankenburg and Zanarini [5] published an original article on 213 participants with BPD who were recruited from an inpatient setting at baseline and at 6 years, 8 years, and 10 years follow-ups (200 participants remained in the study). They assessed BMI as a running average and correlated this measurement with symptomatic outcomes, functional outcomes, and medical outcomes. From baseline to the end, the percentage of obese participants increased from 17 to 34%. With each 5-U increase of cumulative BMI, the risk of medical hospitalization increased 35% and having two or more medical conditions related to weight increased by 60%. Obesity was also significantly correlated with having no partner (23% increased risk), having a GAF score of 60 or less (43% increased risk), and receiving disability benefits (55% increased risk). Hence, for patients with BPD, an increase in cumulative BMI may be a marker for worsened medical comorbidity along with poor symptomatic and functional outcomes [5].

Metabolic syndrome is related to obesity (with the addition of increased blood glucose, dyslipidemia and hypertension) and is a risk factor for both cardiovascular disease and diabetes. Kahl et al. studied 135 inpatients with BPD cross-sectionally in comparison with 1009 primary clinic outpatients. They found double the rate of metabolic syndrome among BPD patients, but, in contrast to other studies reviewed, the two groups had similar BMIs. Unlike many other studies assessing metabolic health and obesity, these authors evaluated psychiatric medication use to investigate contribution to metabolic syndrome. Moreover, instead of self-report, they measured blood pressure, waist circumference and collected blood to quantify fasting metabolic profile of the patients. Their findings were concordant with the general understanding of the risk factors for metabolic syndrome and BPD: patients who were taking second-generation antipsychotics had a higher risk of having metabolic syndrome [6].

The studies reviewed above were conducted with a clinical population whose first presentation was to an inpatient psychiatric facility. In a different approach, Powers and Oltmanns investigated a community-based population of 608 middle-aged participants from Saint Louis (ages 55–64) over two time points 6 months apart to explore the relationship between personality disorders and physical health. They assessed all personality disorders using a modified dimensional method and in particular focused on BPD since it is widely reported to lead to significant functional impairment [7]. They video-recorded the Structured Interview for DSM-IV Personality [8], which orders questions by themes rather than disorders. However, instead of using categorical diagnosis of one of the 10 individual disorders, they collapsed them to a quantification of ‘disordered personality’. They used a category-based approach in determining cluster A (odd-eccentric), B (dramatic-erratic), or C (anxious-fearful) symptoms. BPD was specifically examined. Physical health was evaluated using self-report surveys asking about the number of chronic physical illnesses at baseline (computerized screening version of Diagnostic Interview Schedule) and eight general health constructs (e.g., physical functioning, health perceptions, pain, energy/fatigue utilizing the RAND-36 Health Status Inventory). Correlation and regression analyses were conducted. Overall level of ‘disordered personality’ correlated significantly with number of chronic illnesses at baseline. Pain was increased and general health perceptions, physical functioning and energy level were decreased in relation to Cluster A, B, and C scores and the number of BPD features. Healthcare utilization and medication usage were increased at follow-up significantly for overall disordered personality score, Cluster B score and the number of BPD features. When controlled for recent major depressive disorder, some correlations were no longer significant (e.g., physical functioning and role limitations). However, energy level and general health perceptions remained significant with the highest variance explained by disordered personality. Moreover, disordered personality predicted worsened follow-up outcomes of multiple areas of physical health reported by participants even when controlled for recent MDD, baseline functioning, exercise, smoking, and drinking. Specifically, number of BPD features was a significant predictor of all physical health variables surveyed even when controlled for recent major depressive disorder although the amount of variance that was explained decreased. At follow-up, number of BPD features was uniquely predictive of low-energy and negative health perceptions, but not of pain, physical functioning or role limitations. The limitation of this study was the usage of self-report measures of physical health and the narrow age range of 55–64 [7].

Powers and Oltmanns [9] reported intriguing findings from the same cohort above regarding comorbidities in BPD patients by extending their analyses. Although they assessed physical disorders by self-report as before, this time, they employed three methods of assessing BPD: trained interviewer using a structured interview, an informant report and self-report by patients. The number of participants for whom all three was obtained was 940/1051. In this report, BMI was analyzed in relation to BPD and comorbidities and emerged as a mediator between heart disease and arthritis indicating obesity as a connection between BPD and other health problems. However, the significant association between BPD and heart disease was not observed when personality assessment was performed by a trained interviewer [9].

Although personality disorders usually do not get diagnosed in early adolescence, Chen et al.[10] modified instruments validated for adults and conducted and reported a longitudinal community-based study of 736 individuals from the Children in Community Study which started in 1983 (mean age 13.7) and followed participants over 20 years until 2004 (mean age 33.2) with a retention rate of over 95%. Their objective was to evaluate the impact of Axis I psychiatric disorders and personality disorders on long-term physical health. They observed the highest rates of pain and physical illness among the adolescents who were comorbid with both Axis I disorders and personality disorders (69/736). In this study, authors commented that their analysis suggested that the impact of personality disorders diagnosed in adolescence was stronger than that of Axis I psychiatric disorders. Adolescents with only Axis I disorders and no personality disorders (81/736) were slightly sicker than the adolescents without Axis I or personality disorders (506/736), but the difference was not statistically significant. The annual rate of health decline of the participants with personality disorders was 50% faster than those without either Axis I or personality disorders, even when adjusted for sociodemographic factors. They concluded that only looking at Axis I disorders without taking personality disorders into consideration would underestimate the negative impact of mental health on physical health. Their results were controlled for risky behaviors such as smoking in this population. They cited the use of self-report measures for physical health as a limitation of their study [10].

This same group later reported from the same longitudinal study that, at age 33, this group (n = 621) had an obesity rate of 16.6%. The risk of adult obesity increased significantly with any personality disorders (almost two-fold), and obsessive-compulsive (almost seven-fold), paranoid, and/or histrionic personality disorders detected at adolescence. The authors pointed out that BPD did not reach conventional statistical significance due to the low number of cases [11].

Lee et al. pursued the relationship between personality types and cardiovascular disease further with a longitudinal cohort study. This study was spun off from the National Institute of Mental Health Epidemiological Catchment Area longitudinal study. Two hundred and forty-four participants were assessed over a 23-year follow-up (four waves) for the relationship of DSM-III personality disorders and incidence of cardiovascular health [12]. The respondents’ personality disorders cluster and dimensional traits were calculated as well. 13.3% had a personality disorder including 10% with a Cluster B personality disorders (mostly histrionic personality disorders). Neither Axis I diagnoses (including major depressive disorder) nor any personality disorders at baseline (Wave 1) was associated with incident cardiovascular disorder at Wave 4. However, when Cluster B personality disorders were analyzed separately, they correlated significantly with cardiovascular disease (even when adjusted for presence of smoking and diabetes) and among these only BPD exceeded the statistical significance threshold. All of the participants who had comorbid cardiovascular disease and a personality disorder had a Cluster B personality disorder. Of note, the other clusters had too few subjects to assess with sufficient power. Furthermore, post-hoc analysis indicated that the presence of Cluster B personality disorders at the onset increased the odds of mortality due to coronary heart disease (CHD) longitudinally [12].

Cross-sectionally, Moran et al.[13] similarly reported strong association between BPD and ischemic heart disease utilizing the British National Survey of Psychiatric Comorbidity community-based database from among 8560 people aged 16–74 years. Stroke and ischemic heart disease (based on heart attack, angina, or coronary artery bypass surgery) were self-reported primary vascular outcome measures and personality disorders were assessed with DSM-IV Structured Clinical Interview for Axis II personality disorders. Diabetes, hypertension, smoking, and alcohol use were also assessed and adjusted for. Data available for 8399 participants was analyzed for personality disorders. 2462 participants (28.7%) had a personality disorder. After adjustment for other secondary variables, such as age, diabetes, and hypertension, stroke and ischemic heart disease were significantly more likely to be reported by participants with any personality disorders. After adjusting for comorbidity with other personality disorders, only BPD and Schizoid personality disorders remained significantly associated with ischemic heart disease (stroke correlations were significant only when adjusted for variables other than comorbid personality disorders) [13].

Among 10 573 adults older than 60 years old, when cross-sectionally analyzed using a nationally representative US sample, Pietrzak et al.[14] observed a statistically significant 26% increase in CHD for participants with any personality disorders after controlling for demographics, other well known risk factors and comorbid drug-use, mood, and anxiety disorders. Specifically, CHD and personality disorders correlations were statistically significant for Avoidant, Schizoid, and Obsessive-Compulsive personality disorders diagnoses. The authors pointed out that although participants’ self-report was the basis for physical and personality assessments, an additional confirmation was implemented by asking the participants whether their heart disease was diagnosed by a physician or other healthcare professional [14].

We found only two studies that used objective measurements to assess cardiovascular health. Both were small, cross-sectional and observational. Greggersen et al.[15] studied 47 women with BPD in comparison with 28 age-matched women without BPD. Common carotid artery scanning by ultrasound revealed that, compared with controls, patients with BPD had greater intima–media thickness indicating higher future atherosclerosis and cardiovascular disease risk. This correlation remained statistically significant even when controlled for BMI and physical activity. However, when adjusted for depression and dysthymia, the difference became statistically insignificant [15]. Tully and Selkow, in a noncohort study, identified 30% prevalence of personality disorders diagnosis among 73 heart failure patients (assessed in a cardiology clinic) who were being screened for symptoms of anxiety, depression, and suicidality as part of a referral process. The heart failure patients who also had personality disorders had higher likelihood of comorbidity with major psychiatric disorders, chronic pain, sleep apnea, and diabetes [16].

Three studies of physical and personality disorders comorbidity were conducted making use of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) – one of a handful of large-scale epidemiological surveys that diagnoses personality disorders through face to face interviews yielding an outlying 21% prevalence (including 5.9% BPD):

  1. El-Gabalawy et al.[17] analyzed data from Wave 2 of the almost 35 000-adult nonclinical NESARC sample to study the relationship of BPD with multiple physical health conditions after adjusting for confounders such as demographic variables, Axis I mental disorders or other personality disorders. A strong association emerged indicating that BPD was a statistically significant risk factor for arthritis, hypertension, cardiovascular disease, gastrointestinal disease, sexually transmitted disease or any physical disorder. In this analysis, diabetes, obesity and stroke did not correlate with BPD. This result is opposite to those from other studies that found obesity associated with BPD. Not surprisingly, the comorbidity of BPD and physical disorders predicted poorer quality of life and suicide attempts when compared with BPD alone [17].
  2. Quirk et al.[18] pooled data from Wave 1 and Wave 2 of the NESARC data and looked for correlations with other personality disorders individually and clustered into A, B, and C. They also added to the above study by inspecting younger (<55) and older (≥55) age ranges. In summary, their extensive analysis suggested that age can make a difference in all personality disorders subtypes (with the exception of Narcissistic personality disorders) and clusters and especially BPD such that younger participants with personality disorders are more vulnerable to cardiovascular disease. Arthritis correlated significantly with younger age personality disorders group for all Cluster A personality disorders but individually for Schizoid and Schizotypal personality disorders. Arthritis also correlated with all Cluster B and Cluster C personality disorders regardless of age with the exception of Obsessive-Compulsive personality disorders. Diabetes was associated with any personality disorders, Cluster A personality disorders, and BPD for all age groups. Gastrointestinal disease was significantly correlated with all Cluster A personality disorders as a group and individually with no age modification. All Cluster B personality disorders as a group and individually except Histrionic personality disorders were risk factors for gastrointestinal disease. Cluster C personality disorders enhanced gastrointestinal disease only 25% as a group with no significance at the individual level [18].
  3. The last NESARC study by Goldstein et al.[19] investigated Antisocial Behavioral Syndromes (i.e. Antisocial personality disorder, Conduct Disorder and ‘Adulthood Antisocial Behavior Syndrome’ – a non-DSM entity) in conjunction not only with chronic physical disorders but also hospitalization, injuries and disability. Participants who were diagnosed with Antisocial personality disorder were at increased risk for arthritis after adjustment of confounding covariates. The adjusted risks for liver disease, gastrointestinal disease, injuries, CHD and hospitalization rate and length were all significantly increased with the presence of Antisocial personality disorder. Authors pointed out that findings concerning hospitalization and injuries were consistent with the reckless and impulsive behaviors observed in Antisocial personality disorder despite the limitation that this was a cross-sectional study [19]. The same group reported elsewhere that when BMIs of participants were correlated with Antisocial personality disorder, the analysis revealed a sex by antisocial syndrome interaction when BMI was separately analyzed for men and women. Antisocial personality disorder among women very significantly increased the risk of extreme obesity three-fold after adjustment for confounders [20].

Most recently published original analyses which aimed to elucidate the multimorbidity problem (that is formed by concomitant ‘mental state disorders’ (Axis 1), personality disorders and physical disorders) have utilized data from the Geelong Osteoporosis Study conducted among a random population sample of 765 women (≥25 years) in Southeastern Australia:

  1. In the first study, Quirk et al. cross-sectionally assessed Axis I mental disorders and personality disorders (clustered A, B and C or ‘any’) using structured interviews and a very wide range of physical disorders that were being treated or self-reported along with typical sociodemographic data. This yielded some new associations between personality disorders clusters and different disorders. Briefly, any personality disorders diagnosis was a risk factor for increased syncope and seizures and recurrent headaches. Cluster B personality disorders were correlated with increased risk of arthritis, psoriasis, seizures and syncope. Cluster A personality disorders associated significantly with gastroesophageal reflux disease and syncope and seizures, whereas Cluster C personality disorders were linked to higher propensity for recurrent headaches. More importantly, these links remained significant when adjusted for medications and physical activity [21].
  2. In the second study Quirk et al. addressed the multimorbidity problem by excluding women with only personality disorders and no ‘mental state disorder’ (Axis I). They included 371 controls (no lifetime Axis I or personality disorders), 115 women who had comorbid ‘mental state disorder’ and personality disorders and as the third group 238 women without personality disorders but with an Axis I ‘mental state disorder’. Instead of analyzing for individual diseases or systemic illness groups, they defined ‘physical multimorbidity’ as having more than five lifetime physical health disorders. The analysis demonstrated that having a ‘mental state disorder’ without a personality disorder increased the risk for physical multimorbidity more than two-fold. When a personality disorder was added to the ‘mental state disorder’, the odds increased to four-fold and both associations remained significant when adjusted for covariates [22▪].

Finally, Fok et al. have investigated life expectancy at birth and all-cause mortality among people with personality disorders who were identified from a large psychiatric case register. For 1836 people with personality disorders, life expectancy at birth was almost 20 years shorter than that of the general population (male and female). Compared with the general population the standard mortality ratio was 4.2-fold for all personality disorders patients, five-fold for females, 3.5-fold for males and 10.3-fold for personality disorders patients aged 15–44 years [23].

Due to space and scope restrictions, we have excluded several older similar reports of comorbidities from our review. Moreover, we have only reviewed reports that (mostly categorically) diagnose a personality disorder. A very recent review by Dixon-Gordon et al.[24▪▪] reviews dimensional measures of personality in relation to physical health.

Two older but very comprehensive reviews are available and cover areas we have circumvented due to limitations:

  1. Quirk et al.[25] reviews the epidemiology of the personality disorders and describes the major population-based large-scale epidemiological projects. This review also has a section on healthcare utilization of people with personality disorders.
  2. Dixon-Gordon et al.[24▪▪,26] describe in more detail studies that report the relationship of single physical disorders with personality disorders (individual or clustered) and includes insomnia, migraine etc.

Soeteman et al.[27] reports the analysis of economic impact of personality disorders on the society utilizing a multisite 1740-person database.

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Recent findings have extended and clarified the conclusions of Frankenburg and Zanarini [4]. There was a strong association between personality disorders and physical disorders in cross-sectional and community-based studies. Longitudinal data have now shown that severity of any personality disorders is both associated with physical ill-health at baseline and also predictive of worsening physical health from a variety of disorders. In addition, the severity of any personality disorders is more strongly predictive of physical, mental, and social ill-being than is any particular subtype or cluster of personality disorders. This confirms that all personality disorders share certain deficiencies in self-regulation of behavior, which distinguish unhealthy personalities from healthy personalities [28,29▪▪,30▪▪]. A healthy personality is described in the alternative criteria of DSM-5 in terms of high self-directedness (i.e., healthy identity with ‘self-direction’ and ‘self-esteem’) and high Cooperativeness (i.e., healthy interpersonal relations with ‘intimacy’ and ‘empathy’) [31]. More generally, the self-regulatory components of a healthy personality include dimensions of self-directedness (i.e., purposeful, responsible vs. aimless, blaming), cooperativeness (i.e., helpful, empathic vs. hostile, revengeful), and self-transcendence (i.e., altruistic, moderate vs. individualistic, self-serving), as measured by the Temperament and Character Inventory [28,32]. These self-regulatory features of personality determine the presence and severity of any personality disorders, as well as predicting risk of comorbid physical disorders [28,29▪▪,30▪▪,33–36].

These observations have important implications for understanding the comorbidity of physical, mental, and social dysfunction with personality disorders. Rather than focusing on discrete disorders in different organ systems, the findings suggest that we should also consider the overall functioning of the person as a whole organism. It has often been suggested that the association between personality disorders and physical diseases is mediated by lifestyle behaviors, such as smoking, drinking, diet, and risk-taking behaviors [37–39]. However, recent genetic data show that the regulatory genes for human personality are also expressed throughout most organ systems, and they are involved in regulating the healthy co-expression of complex sets of genes in brain and most other organs to promote healthy longevity and plasticity in response to changing goals, values, and environmental challenges [29▪▪,30▪▪].

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We would like to thank Gail K. Dokucu for her assistance with the study.

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Financial support and sponsorship

The work was supported by the Zell Family Foundation Scholar Award to MED.

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Conflicts of interest

There are no conflicts of interest.

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Papers of particular interest, published within the annual period of review, have been highlighted as:

  • ▪ of special interest
  • ▪▪ of outstanding interest
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The article looks at the more severe aspects of comorbidity among personality disorders, other mental disorders and physical disorders by defining lifetime number of more than five physical disorders as ‘physical multimorbidity’ and showing that personality disorders add a significant level of severity to this risk when comorbid with other mental disorders.

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This is a thematic review that complements our work by summarizing the studies which report on the correlation of personality dimensions (not disorders) with physical health. In addition, it summarizes multiple small association studies with single health problems (insomnia, migraines etc.).

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The large genome-wide association study identified and replicated over 700 genes for the self-regulatory aspects of personality which largely determine a person's overall risk for both physical and mental health.

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The large genome-wide study identified and replicated another 700 genes for human temperament, which influence the risks of particular types of physical and mental disorders.

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antisocial personality disorder; borderline personality disorder; comorbidity; diabetes mellitus; eating disorder; iatrogenic disease; multimorbidity; obesity; personality disorder; polymorbidity

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