The Critical Relationship Between Anxiety and Depression.

Anxiety and depressive disorders are among the most commonpsychiatric illnesses; theyarehighly comorbidwith each other, and together they are considered to belong to the broader category of internalizing disorders. Based on statistics from the Substance Abuse andMental Health Services Administration, the 12-monthprevalenceofmajordepressive disorder in 2017was estimated to be 7.1% for adults and 13.3% for adolescents (1). Data for anxietydisorders are less current, but in 2001–2003, their 12-month prevalence was estimated to be 19.1% in adults, and 2001–2004 data estimated that the lifetime prevalence in adolescents was 31.9% (2, 3). Both anxietyanddepressivedisorders aremoreprevalent inwomen, with an approximate 2:1 ratio in women compared with men during women’s reproductive years (1, 2). Across all psychiatric disorders, comorbidity is the rule (4), which is definitely the case for anxiety and depressive disorders, as well as their symptoms. With respect to major depression, a worldwide survey reported that 45.7% of individuals with lifetime major depressive disorder had a lifetime history of one or more anxiety disorder (5). These disorders also commonly coexist during the same time frame, as 41.6% of individuals with 12-month major depression also had one or more anxiety disorder over the same 12-month period. From the perspective of anxiety disorders, the lifetime comorbidity with depression is estimated to range from 20% to 70% for patients with social anxiety disorder (6), 50% for patients with panic disorder (6), 48% for patients with posttraumatic stress disorder (PTSD) (7), and 43% for patients with generalized anxiety disorder (8). Data from the well-known Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study demonstrate comorbidity at the symptom level, as 53% of the patients with major depression had significant anxiety and were considered to have an anxious depression (9). Anxietyanddepressivedisorders aremoderatelyheritable (approximately 40%), and evidence suggests shared genetic risk across the internalizing disorders (10). Among internalizing disorders, the highest level of shared genetic risk appears to be between major depressive disorder and generalized anxiety disorder. Neuroticism is a personality trait or temperamental characteristic that is associated with the development of both anxiety and depression, and the genetic risk fordevelopingneuroticismalsoappears tobe sharedwith that of the internalizing disorders (11). Common nongenetic risk factors associated with the development of anxiety and depression include earlier life adversity, such as trauma or neglect, aswell asparenting styleandcurrent stressexposure. At the level of neural circuits, alterations in prefrontal-limbic pathways that mediate emotion regulatory processes are common to anxiety and depressive disorders (12, 13). These findings are consistentwithmeta-analyses that reveal shared structural and functional brain alterations across various psychiatric illnesses, including anxiety andmajor depression, in circuits involving emotion regulation (13), executive function (14), and cognitive control (15). Anxiety disorders and major depression occur during development,withanxietydisorders commonlybeginningduring preadolescence and early adolescence and major depression tendingtoemergeduringadolescenceandearlytomid-adulthood (16–18). In relation to the evolution of their comorbidity, studies demonstrate that anxiety disorders generally precede the presentation of major depressive disorder (17). A European community-based study revealed, beginning at age 15, the developmental relation between comorbid anxiety and major depression by specifically focusing on social phobia (based on DSM-IV criteria) and then asking the question regarding concurrent major depressive disorder (18). The findings revealed a 19% concurrent comorbidity between these disorders, and in 65% of the cases, social phobiaprecededmajordepressivedisorderbyat least 2 years. In addition, initial presentation with social phobia was associated with a 5.7-fold increased risk of developing major depressive disorder. These associations between anxiety and depression can be traced back even earlier in life. For example, childhoodbehavioral inhibition in response to novelty or strangers, or an extreme anxious temperament, is associated with a threeto fourfold increase in the likelihood of developing social anxietydisorder,which in turn is associated with an increased risk to develop major depressive disorder and substance abuse (19). It is important to emphasize that the presence of comor‐ bid anxiety symptoms and disorders matters in relation to It is important to remember that these disorders are highly comorbid and that their symptoms are frequently not separable.