{mosimage}Stephen Soreff, MD
Boston University
{mosimage}Patricia Bazemore, MD
University of Massachusetts Medical School
INTRODUCTION
The comorbidity of major depressive disorder (MDD) and anxiety disorders has prompted a new examination of their relationship. Research into the epidemiology, genetics, and psychodynamic factors that affect people with these disorders has demonstrated statistical linkages between depression and anxiety. Practitioners frequently observe firsthand the comorbidity of MDD and anxiety disorders, as they are both common entities. These findings have important clinical implications that influence the day-to-day management of patients. This article discusses the extent of the comorbidity, looks at the genetic evidence for viewing these 2 disorders as a single condition, explores the common personality features among people with these disorders, and highlights management recommendations. While MDD and specific anxiety disorders, specifically generalized anxiety disorder (GAD), were once seen as separate and distinct diagnoses, it’s possible that they should be considered a single entity.
THE EPIDEMIOLOGY OF COMORBIDITY
Extent of comorbidity of psychiatric diagnoses in general
High rates of comorbidity exist for psychiatric diagnoses in general, but the rate of comorbidity is particularly high for depression and anxiety. Kessler, in a major prevalence study involving 9,283 participants and all psychiatric diagnoses, found that 22% of those interviewed had 2 psychiatric diagnoses, and 23% had 3 or more diagnoses.1
Comorbidity of MDD and anxiety spectrum disorders
MDD is comorbid with the anxiety spectrum as a whole. In a large study of adolescent outpatients with a depressive disorder, over 70% also had an anxiety disorder.2 In another study of patients with social anxiety disorder (SAD) comorbidities, SAD was most frequently coupled with MDD.3 Attention-deficit/hyperactivity disorder (ADHD) is also a common comorbidity of MDD; patients with MDD have an ADHD prevalence of 9.4%.4 MDD is also present in 30-43% of patients with obsessive-compulsive disorder (OCD).5 Additionally, the National Comorbidity Survey Replication (NCS-R) demonstrated that the relationship between MDD and panic disorder, agoraphobia, specific phobia, social phobia, GAD, posttraumatic stress disorder, and OCD had been established at the P < .05 level.1
Comorbidity of MDD and GAD
In a remarkable study, Moffitt followed up with 1,037 participants in Dunedin, New Zealand for 32 years (96% retention rate). Moffitt found that, in 37% of people with depression, an anxiety diagnosis commenced either before or at the same time as the depression diagnosis. For those with a lifetime depression diagnosis, 48% had a history of anxiety.6 Furthermore, 72% of those with a lifetime anxiety diagnosis had depression in their histories.
Researchers have shown the association between MDD and GAD in other studies, as well. Kendler reports that GAD and MDD “are highly co-morbid in both clinical and epidemiological studies.”7 GAD is frequently found with any mood disorder. In an elderly population, 80% of those with a diagnosis of GAD also had a mood disorder.8 And “up to 80% of subjects with lifetime GAD also have a comorbid mood disorder during their lifetime.”9
GENETIC BASIS OF COMORBIDITY
In the last several years, numerous studies have demonstrated a genetic relationship between MDD and specific anxiety disorders. The most compelling evidence is available for a relationship between MDD and GAD. Kendler found a strong correlation between lifetime risk for MDD and GAD based on personal interviews with more than 37,000 twins from the Swedish twin registry. He reported that “genetic risk factors for a lifetime diagnosis of MDD and GAD are strongly correlated, with higher correlations in women than men.”7 The genetic correlation was estimated to be +1.00 for the women in the study and +0.74 for the men. Additional twin studies, such as the one by Ehringer, who looked at 1,162 adolescent twins and 426 of their siblings, emphasized the genetic basis of both MDD and GAD.10 In his review article, Levinson noted that “there may be common genetic factors that can predispose to MDD, neuroticism, and general anxiety disorder….”11
This growing evidence points toward genetic pleiotropy, ie, that one gene causes both MDD and GAD. The research indicates a shared physiological and psychological mechanism. The result is common gene vulnerability to stress and other environmental contributors to MDD and GAD.9
PSYCHODYNAMIC FACTORS RELATING TO COMORBIDITY
Some studies, such as that of Weinstock, suggest that neuroticism is the psychological factor that predisposes an individual to both MDD and anxiety disorders. In the Weinstock study, this factor is linked to people who have MDD and GAD, specifically.12 In a study of 1,200 outpatients completing the Penn State Worry Questionnaire (PSWQ), Chelminski found that the highest incidence of worrying was in the GAD group. Patients with depression and patients with anxiety disorders also shared higher scores than patients in the general population and those who were not anxious.13 Worrying is a common denominator in both patients with depression and patients with anxiety disorders.
COMORBIDITY MANAGEMENT CONCERNS
Treating patients with comorbid depression and anxiety requires increased vigilance compared with treating patients who have a single disorder. Concerns include increased disease severity, heightened suicide potential, and higher rates of cardiovascular problems. Tukel reports that patients with comorbid OCD and MDD had more severe OCD symptoms than if they had had OCD alone.5 Patients aged 60 years or older with both GAD and depressive disorders had a greater risk of suicide than those with GAD alone.8 Stein did a study of 13,085 patients in a large managed care setting who had both an anxiety diagnosis and an antidepressant prescription. The study showed that 57% of patients in a 6-month period were not compliant with the prescribed medication regime. Adherence to the antidepressant regimen was improved if mental health specialists followed the dually diagnosed patients.14
The treating physician should keep in mind the potential impact of comorbid depression and anxiety on other medical conditions that the patient may have or for which the patient may exhibit an increased risk. Both MDD and GAD increase the risk of cardiovascular problems. Patients with depression, anxiety, and anger had higher cholesterol levels than those without these findings. The risk of coronary artery disease is higher in patients with comorbid anxiety or hostility and depression than in those with depression alone.8 Patients with both MDD and GAD have greater abnormalities in their lipid profiles than patients with either MDD or GAD alone. Therefore, patients in the comorbidity group have “greater risk of mortality from coronary artery disease (CAD) than do patients with either depression or anxiety disorder.”15 The comorbid presence of anxiety and depression may also occur following myocardial infarction, which shows that cardiovascular disease may actually cause the dual diagnosis as well as result from it.16 As these observations suggest, patients with both MDD and GAD clearly require increased concern, monitoring, and intervention by a responsible clinician.
CONCLUSION
The genetic, epidemiological, and clinical evidence indicates the presence of a strong relationship between MDD and anxiety disorders. A particularly strong relationship between MDD and specific anxiety disorders such as GAD has been established through research. Some experts in the field, such as Moffitt, recommend the term “stress disorder” to refer to the group of individuals who are diagnosed with both MDD and GAD.6 The comorbidity of MDD and anxiety disorders in many patients has important clinical implications that influence the day-to-day management of patients.
REFERENCES
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