ﺑﺎﺯﮔﺸﺖ ﺑﻪ ﺻﻔﺤﻪ ﻗﺒﻠﯽ
خرید پکیج
تعداد آیتم قابل مشاهده باقیمانده : 3 مورد
نسخه الکترونیک
medimedia.ir

Comorbid anxiety and depression in adults: Epidemiology, clinical manifestations, and diagnosis

Comorbid anxiety and depression in adults: Epidemiology, clinical manifestations, and diagnosis
Literature review current through: Jan 2024.
This topic last updated: Jul 22, 2022.

INTRODUCTION — Anxiety disorders and depressive disorders are highly prevalent conditions that frequently co-occur. Individuals affected by both anxiety and depressive disorders concurrently have generally shown greater levels of functional impairment, reduced quality of life, and poorer treatment outcomes compared with individuals with only one disorder.

Studies of the clinical presentation, course, assessment, and diagnosis of these conditions have largely focused on the co-occurrence of depression and generalized anxiety disorder. The diagnosis of these conditions is complicated by the presence of mixed anxiety and mood states as well as substantial overlap in physical and emotional symptoms of the disorders. Anxious distress was included as a subtype of major depression in the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) [1].

This topic describes the epidemiology, pathogenesis, clinical manifestations, course, and diagnosis of comorbid anxiety and depression. The epidemiology, pathogenesis, clinical manifestations, course, diagnosis, and treatment of individual depressive and anxiety disorders are described separately.

(See "Unipolar depression in adults: Epidemiology".)

(See "Unipolar depression in adults: Assessment and diagnosis".)

(See "Unipolar depression in adults: Course of illness".)

(See "Generalized anxiety disorder in adults: Epidemiology, pathogenesis, clinical manifestations, course, assessment, and diagnosis".)

(See "Social anxiety disorder in adults: Epidemiology, clinical features, assessment, and diagnosis".)

(See "Obsessive-compulsive disorder in adults: Epidemiology, clinical features, and diagnosis".)

(See "Panic disorder in adults: Epidemiology, clinical manifestations, and diagnosis".)

(See "Agoraphobia in adults: Epidemiology, pathogenesis, clinical manifestations, course, and diagnosis".)

EPIDEMIOLOGY

Population-based samples — There is a high rate of comorbid anxiety and depressive disorders in population-based samples. The lifetime prevalence of anxiety disorders and major depression among adults in the United States has been reported to be 28.8 percent and 16.6 percent, respectively [2].

Three international studies found that depression is significantly associated with every anxiety disorder [2-4], with the highest associations in patients with generalized anxiety disorder (GAD) and the lowest in those with agoraphobia and specific phobias.

Lifetime prevalence of comorbid anxiety and depression in the general population is very high [5-11]. As examples:

In a study of 1783 individuals, 75 percent of those with depression met criteria for an anxiety disorder in their lifetime; 79 percent of those with an anxiety disorder met criteria for lifetime major depression (table 1) [5].

A study of 74,045 adults across 24 countries found an average lifetime prevalence of DSM-IV/Composite International Diagnostic Interview major depressive disorder (MDD) of 11.2 percent; 45.7 percent of those individuals also had one or more lifetime anxiety disorders [7].

A study of 20,013 United States adults with unipolar MDD found lifetime prevalence rates of SAD to be 0.77 percent and an anxiety disorder other than SAD to be 3.71 percent [11].

A study found that the 12-month prevalence of comorbid mood and anxiety disorders (3.5 percent) in the Netherlands was higher than the prevalence of a pure mood disorder (ie, a mood disorder without a co-occurring anxiety disorder, eating disorder, or schizophrenia; 3.1 percent) but lower than pure anxiety disorder (7.7 percent) [12]. Of patients with mood disorders, 60.5 percent were diagnosed as having another mental disorder. Anxiety disorders were the most common category of disorders, with a prevalence of 54.3 percent among patients with a co-occurring disorder.

Clinical samples — High rates of comorbidity between anxiety disorders and depression have been observed in samples of patients receiving mental health care.

Studies of patients with anxiety disorders have yielded a point prevalence of comorbid depression ranging from 2 to 69 percent, with lifetime rates as high as 81 percent [13-18].

Examples include:

In a sample of 1127 outpatients with anxiety disorders, current and lifetime prevalence rates of mood disorders were 57 and 81 percent, respectively [16]. In those with a primary anxiety disorder, 30 percent met criteria for a comorbid mood disorder (major depression and/or dysthymia). The prevalence of comorbid major depression ranged from 3 percent in specific phobia to 69 percent in posttraumatic stress disorder.

In a sample of 223 outpatients from a general hospital in Korea with MDD, 33 percent were found to have a comorbid panic disorder [17].

Small studies of samples of patients with depressive disorders have yielded variations in the point prevalence of comorbid anxiety of 44.7 to 92.1 percent [19-21].

In an analysis of 255 depressed outpatients, 44.7 percent met diagnostic criteria for an anxiety disorder [21].

In a sample of 72 inpatients with major depression, 54.1 percent met diagnostic criteria for at least one anxiety disorder [20].

In a sample of 120 depressed patients who were participating in a genetics study, the odds of having a comorbid anxiety disorder with “familial” MDD were 6.6 (95% CI 3.8-11.4, p <0.001) [22].

Risk factors — Analyses of data of 3021 individuals from the Early Developmental Stages of Psychopathology study have been used to assess risk factors, temporal patterns, and longitudinal outcomes of anxiety, depression, and co-occurring anxiety and depressive disorders [23].

A study examined the relationship between risk factors for anxiety disorders compared with depressive disorders and with co-occurring anxiety and depressive disorders [23]. Factors common to both disorder classes were: female gender, perinatal factors, and parental psychiatric history. Risk factors for the co-occurrence were a direct combination of the risk factors for either disorder alone. There were no risk factors detected specific to comorbid anxiety and depression that were not risk factors for the individual disorders as well.

The risk of depression in individuals with anxiety disorders was significantly associated with female gender, number of anxiety disorder diagnoses, severity of anxiety disorder at baseline, and the presence of panic attacks [24].

In older adults, risk factors for comorbid anxiety in late-life depression have been found to include lower age, female sex, less education, higher depression severity, early traumatization, neuroticism, extraversion, conscientiousness, and socioeconomic stressors [25,26].

A study of 1024 Chinese outpatients found that individuals with co-occurring MDD and GAD, compared with those with MDD without co-occurring GAD, were more likely to be female, have a marital status of “other” (single, divorced, widowed, separated), be depressed, have poor physical and psychological quality of life, have less objective support, and have poor sleep quality [18].

An epidemiological study of a nationally representative sample of 7076 adults in the Netherlands found the following factors to be associated with co-occurring anxiety and mood disorders compared with either disorder in its pure form [12]:

Female gender

Younger age (25 to 34 years)

Lower education level

Living alone

Unemployment

Parental psychiatric history

Childhood trauma

PATHOGENESIS — While our understanding of the etiology of co-occurring anxiety and depression is limited, research has identified similarities between the two disorders in their neurobiology, genetic structure, and presence of neuroticism and harm avoidance.

Neurobiology — Research findings suggest that mood and anxiety symptoms result from a disruption in the balance of impulses from the brain’s limbic system. A 2015 study reported that individuals with comorbid depression and anxiety have increased resting-state functional connectivity of the limbic network when compared with depression or anxiety alone [27].

Brain imaging studies have most consistently implicated the amygdala, anterior cingulate cortex, and insula in the pathophysiology of anxiety [28]. As examples, neuroimaging studies in posttraumatic stress disorder (PTSD), social phobia, and specific phobia found significant hyperactivity in the amygdala and insula across all three disorders [29]. Neuroimaging studies in depression have not been as consistent. Evidence suggests abnormal activity levels in the anterior cingulate, dorsolateral, medial and inferior prefrontal cortex, insula, superior temporal gyrus, basal ganglia, and cerebellum.

The most consistent abnormality across both disorder classes has been found to be hyperactivity within the amygdala. This hyperactivity appears to manifest differently in anxiety and depression. In depressed patients, baseline amygdalar activity is higher than healthy controls; however, in patients with anxiety disorders, amygdalar activation is higher only during provocation tasks [30]. Event-related potential evidence has shown that when compared with patients with anxiety disorder or depression alone, comorbid patients have abnormal frontal-greater-than-parietal P3b topography in the right hemisphere and the highest P3a amplitude at frontal and central sites. In addition, comorbid patients presented decreased activity in the cingulate gyrus, right perirhinal cortex, and right posterior parietal cortex, and increased activity in the left prefrontal cortex and left insular cortex [31].

Individuals with comorbid depression and anxiety have also been found to have lower levels of omega-3 polyunsaturated fatty acids. These levels appear to decrease as anxiety severity increases [32].

Neuropsychological factors — Personality traits and neuropsychological factors may play a role in the risk for co-occurring depression and anxiety disorders. In two large-scale studies, neuroticism was found to be the strongest and most significant predictor of comorbidity between different disorders, particularly anxiety and depression [33,34]. One of the studies examined whether comorbid anxiety and depression differed from either disorder cluster alone on neuropsychological and genetic dimensions, finding that those with the co-occurring disorders had:

Greater impairments in working memory and attention compared with those with an anxiety disorder alone.

Higher levels of harm avoidance and neuroticism compared with patients with depression alone, anxiety alone, or substance and alcohol disorders alone.

A study of 74,045 adults across 24 countries found that the severity of role impairment (home management, ability to work, social life, and close relationships) and suicidal ideation were higher in those with co-occurring major depressive disorder (MDD) and anxiety compared with those with MDD alone [7].

A study of 223 Korean outpatients found that individuals suffering from co-occurring MDD and panic disorder had increased impulsivity and more severe suicidal ideation compared with those with MDD alone [17].

A greater likelihood of having two distinct genetic markers for harm avoidance (catechol-O-methyltransferase Met158 and brain derived neurotrophic factor Met66) compared with either disorder alone [35].

Genetics — Two studies suggest that the comorbidity between anxiety (generalized anxiety disorder [GAD] in particular) and depressive disorder could be explained in part by similarities in genetic structure.

A study of more than 5600 same-sex twin pairs attempted to decipher the heritability of common psychiatric disorders [36]. Multivariate twin modeling analysis was used to examine clustering of DSM-III-R symptoms. Vulnerability to these phenotypes could be grouped into two clusters for anxiety and depression. The first cluster described risk for depression and generalized anxiety disorder while the second cluster described a broad risk for phobic disorders. Risk for panic disorder was shared by both clusters.

Another analysis of same-sex twin pairs from the Virginia Twin Study showed a similar two-factor structure, with GAD, panic, agoraphobia and, to some extent, social anxiety disorder in one cluster and specific phobias in another [37].

Twin studies have suggested that the anxiety disorders and major depression were distinct entities and not simply phases of the same disease [38]. A possible explanation for the comorbidity between anxiety and depression is a common genetic etiology and the presence of neuroticism, with environmental factors playing a small role [38].

FK506 binding protein 51 (FKBP5) is a co-chaperone binding protein which modulates the function of glucocorticoid receptors. In a study examining allelic variants of FKBP5, the T allele was more frequent among patients with comorbid depression and anxiety [39].

In a study examining females with the fragile X premutation gene (ie, FMRI gene), 43 percent reported comorbid history of depression and anxiety. Comorbid women had the highest number of CGG repeats in the gene [40].

Conceptual issues — Anxiety and depression overlap in some cognitive components and clinical symptoms (table 2). In the tripartite model of emotion, a prevailing conceptual theory for emotional disorders, anxiety and depression can be deconstructed into three principal components: negative affect, physiologic hyperarousal, and low positive affect [41].

Negative affect encompasses a wide range of negative emotional responses from fear and distress to disgust and anger. Negative affect is seen in both anxiety and depression.

Low positive affect describes a state lacking positive emotional responses, such as happiness or pleasure. Positive emotional responses are absent in depression, but not in anxiety disorders.

Physiologic hyperarousal is characteristic of anxiety disorders but not depression. Signs and symptoms include excessive agitation, edginess, and feeling “keyed up” or tense.

Overlap between anxiety and depression can be partially explained by the shared concept of negative affect. This conceptualization was supported in a study of outpatients with moderate levels of psychopathology and DSM-III diagnoses of major depression (262 patients), dysthymia (82), panic disorder (156), or generalized anxiety disorder (79) [42]. Factor analysis found 12 symptom components.

Depression was best explained by the presence of:

Negative self-view

Anhedonia

Dysphoria

Anxiety was best explained by the presence of:

Panic attacks

Threatening thoughts

Subjective worry and tension

Negative affect (eg, anhedonia, worry, and tension) was shared by both depression and anxiety. Physiologic hyperarousal (panic attacks) was unique to anxiety. Low positive affect (dysphoria) was unique to depression. Among all the factors, negative self-view had the largest influence, accounting for 17.1 percent of the variance seen in anxiety and depression.

The study showed areas of symptom overlap between anxiety and depression. Using the factor structure to predict each diagnosis, strong reliability was found for major depression and panic disorder. However, two-thirds of those diagnosed with GAD were misclassified as having panic disorder or major depression, indicating substantial overlap in symptoms.

A similar pattern of symptom overlap in major depression and anxiety disorders has been seen in other outpatient samples. An analysis of mean scores on anxiety and depression rating scales in 126 outpatients referred to an anxiety specialty clinic found substantial overlap between the two disorder classes [43]. Patients with major depression scored significantly higher on the anxiety scale than those with social phobia. Patients with major depression and patients with obsessive-compulsive disorder had the highest scores on the depression rating scale, with no differences observed among patients with one of the other anxiety disorders.

CLINICAL MANIFESTATIONS — Study of the clinical presentation of anxiety co-occurring with depression has largely focused on symptoms of generalized anxiety disorder. Co-occurring generalized anxiety disorder (GAD) and depression can present on a continuum, from principally anxiety symptoms to mixed anxiety and depression, to principally depressive symptoms.

Some of the symptoms of GAD and depression are characteristic of both disorders, while others are specific to GAD or depression (table 2) [44]:

Symptoms specific to depression:

Loss of interest

Weight change

Poor appetite

Bradykinesia

Guilt or worthlessness

Thoughts of death

Symptoms common to GAD and depression:

Dysphoric mood

Irritability

Agitation or restlessness

Concentration difficulties

Insomnia

Fatigue

Symptoms specific to GAD:

Excessive worry

Autonomic hyperactivity

Exaggerated startle response

Muscle tension

COURSE — Comorbid anxiety (symptoms of generalized anxiety disorders or GAD) and depressive disorders have been found to differ from the individual disorder categories in age of onset [2,21,45], life course [46], and treatment outcome. Presence of both disorders together significantly decreases the odds of recovery, increases the time to therapeutic onset for pharmacotherapy [2,23], and is associated with a more chronic course [47,48], higher symptom severity, and more functional impairment [11,49]. However, the course of the co-occurring conditions can be complex.

Onset and life course — Age of onset patterns for anxiety and mood disorders appear distinct. In a 2005 nationally representative epidemiological study in the United States, the median age of onset was 11 years for anxiety disorders and 30 years for mood disorders [2].

Data from the Early Developmental Stages of Psychopathology (EDSP) study found that [23]:

Onset of anxiety was most likely to occur early in life, with few new cases after age 20

Prevalence of major depression increased significantly after age 20

Age of onset for comorbid anxiety and depressive disorders varied depending on which disorder class was used as the indexing disorder. For an anxiety disorder with comorbid depression, age of onset for the comorbid conditions closely followed that of an anxiety disorder alone. The age of onset for a depressive disorder and comorbid anxiety disorder closely followed that of a depressive disorder alone.

Age of onset appears to vary by anxiety disorder. Subsequent EDSP analysis with additional follow-up data found that age of onset for GAD, panic disorder, and agoraphobia was generally in adolescence and early adulthood (similar to depression), while social anxiety disorder and specific phobias began in early childhood [45]. In a study of 255 depressed outpatients, 44.7 percent met diagnostic criteria for an anxiety disorder. The onset of both social anxiety disorder and GAD was more likely to precede the development of major depression, with the opposite being true for obsessive-compulsive disorder (OCD), panic disorder, agoraphobia, and simple phobias [21].

Co-occurrence of anxiety and depression is associated with a more chronic course compared with either disorder alone [47]. Analysis of data from a nationally representative epidemiologic study in the United States found that, compared with individuals without GAD, patients with a primary lifetime diagnosis of GAD had an increased likelihood of both subsequent onset and persistence of a major depressive episode (MDE). A primary lifetime diagnosis of an MDE predicted the onset but not persistence of GAD. The study found that a temporal association between an MDE and GAD was highest among respondents aged 15 to 24 years. More than one-third of individuals with co-occurring MDE and GAD experienced the onset of both disorders within the same year. Despite the more chronic presentation, few differences in functional impairment have been observed between comorbid anxiety and depression and either disorder alone [21].

Depression is generally episodic in nature with modest rates of recovery, but rates of relapse are high. Anxiety disorders conversely tend to be chronic and unremitting, with low levels of recovery and moderate levels of relapse [46].

A younger age of onset for the first mental disorder was found in those with major depressive disorder (MDD) comorbid with SAD compared with a comorbidity with any other anxiety disorder or to MDD alone [11]. MDD-SAD patients also demonstrated an earlier age of onset for the first depressive episode and an earlier onset of MDD compared with those who had MDD alone.

In a similar study comparing individuals with lifetime MDD and anxiety disorder comorbidity, 68 percent reported an earlier age of onset of an anxiety disorder while 13.5 percent reported an earlier age of onset of MDD. The authors suggest that temporally primary comorbid anxiety may be a large factor in predicting MDD persistence and onset [7].

Co-occurring anxiety disorders and depression may have a worse course than the anxiety disorder alone:

In a 12-year prospective study of patients with GAD or panic disorder with or without agoraphobia, those with comorbid major depression were half as likely to recover, compared with either disorder alone [46].

Data from the National Epidemiologic Survey of Alcohol and Related Conditions study indicated that those with GAD and major depression were significantly more impaired in perceived mental health quality and social functioning, compared with those with GAD alone [50].

A 15-year prospective analysis found that prevalence of anxiety and depression together did not change over the course of the study, while prevalence of anxiety alone and depression alone increased over time [51]. This finding suggests that comorbid anxiety and depression is a more stable condition than either disorder alone. Once comorbidity develops, it is unlikely that an individual will experience a recurrence of either disorder alone, particularly anxiety.

In a community sample of 915 women age 42 to 52 years, women with a lifetime history of a co-occurring anxiety disorder and major depression were more likely to report a history that included recurrent major depression, multiple lifetime anxiety disorders, higher rates of treatment seeking, and current elevations in current anxiety and depressive symptoms, compared with women without a history of an anxiety disorder or major depression occurring concurrently or separately [8].

Treatment response — The presence of both depression and anxiety appears to have a poorer response to treatment than either disorder individually:

In the Sequenced Treatment Alternative to Relieve Depression trial, outpatients with anxious depression (ie, a diagnosis of major depression and an anxiety/somatization subscale score greater than seven on the Hamilton Rating Scale for Depression) had significantly lower response and remission rates and poorer outcomes, compared with patients with non-anxious depression [52,53]. Depressed patients with anxiety took longer to improve than depressed patients without anxiety [54].

In multiple clinical trials of patients diagnosed with anxiety disorders (GAD, panic disorder, social anxiety disorder, and OCD), the presence of co-occurring depression has been associated with poorer response of the anxiety disorder to pharmacotherapy and psychotherapy, compared with those with the anxiety disorders alone [55-59]. These trials suffered from several methodologic limitations, including that participants with comorbid depression had more severe symptoms of anxiety at baseline in some of the trials. Findings on functional outcomes and change in depressive symptoms were mixed.

ASSESSMENT AND DIAGNOSIS — A diagnostic assessment for potential co-occurring anxiety disorders and depressive disorders should include careful patient history, a complete physical examination, and appropriate laboratory studies. The medical history should address medical illnesses, medication side effects, and substance use or withdrawal that can produce anxiety or anxiety-like symptoms (table 3 and table 4) or depressive symptoms. (See "Unipolar depression: Pathogenesis", section on 'Secondary depression'.)

The psychosocial history should screen for stressful life events, family psychiatric history, current social history, substance use history (including caffeine, nicotine, and alcohol), and past sexual, physical, and emotional abuse, or emotional neglect.

Diagnoses of co-occurring depressive and anxiety disorders are based on DSM-5 criteria for the individual disorders [1]. Two syndromes – mixed anxiety and depression, and anxious depression – include symptoms of anxiety, depression, or both that are beneath the threshold required by DSM-5 criteria for individual anxiety or depressive disorders. These emerging constructs may prove to be clinically useful, but require further research.

After diagnoses of both depression and an anxiety disorder have been made, the primary diagnosis should be established. The disorder incurring the greatest distress and impairment to the individual is typically considered the primary diagnosis.

Co-occurring depression and anxiety disorders — DSM-5 diagnostic criteria for depression and anxiety disorders are described below.

Major depressive disorder (MDD) (table 5)

Dysthymia (table 6)

Generalized anxiety disorder (GAD) (table 7)

Obsessive-compulsive disorder (OCD) (table 8)

Panic disorder (table 9)

Social anxiety disorder (table 10)

Specific phobia (table 11)

Agoraphobia (table 12)

PTSD and OCD, classified as anxiety disorders in DSM-IV, were moved to newly formed categories of their own in the revision to DSM-5 [1]. Co-occurring PTSD and depression is discussed separately. (See "Posttraumatic stress disorder in adults: Epidemiology, pathophysiology, clinical features, assessment, and diagnosis".)

Major depressive disorder with anxious distress — Anxious distress was included as a specifier of major depression in DSM-5 [1]. Anxious distress is characterized by the presence of two or more of the following symptoms during most days of the depressive episode (see "Unipolar depression in adults: Assessment and diagnosis", section on 'Depressive episode subtypes (specifiers)'):

Feeling keyed-up or tense

Feeling unusually restless

Difficulty concentrating because of worry

Fear that something awful will happen

Feeling that the individual might lose control of themselves

DSM-5 criteria characterize the current severity of anxious distress as follows:

Mild: Two symptoms

Moderate: Three symptoms

Moderate-severe: Four to five symptoms

Severe: Four to five symptoms with motor agitation

Analyses of data from the Sequenced Treatment Alternative to Relieve Depression clinical effectiveness trial [52,60] have supported the diagnosis of major depressive disorder with anxious distress. In an analysis of data on 1450 outpatients meeting DSM-IV-TR criteria for major depression, 46 percent had a Hamilton Rating Scale for Depression anxiety/somatization subscale score ≥7. Compared with depressed patients without high levels of anxiety, these patients were more likely to be [60]:

Older

Less educated

Severely depressed

Suicidal

Their rates of treatment response and remission were significantly lower, with a greater time to the onset of a clinical response [54]. High levels of anxiety have generally been associated with increased suicide risk, longer duration of illness and greater likelihood of treatment non-response. These results support the addition of the anxious distress specifier to diagnostic criteria for major depression.

DSM-5 does not require patients with comorbid anxiety disorders to be excluded when diagnosing a patient with major depressive disorder with anxious distress. There is some concern among experts that use of the anxious distress specifier may lead clinicians to forget about diagnosing comorbid anxiety disorders under the assumption that the “anxious distress” sufficiently characterizes the clinical presentation of the patient. Clinicians should instead be prompted by the use of the specifier to then take the next step of assessing the patient for a comorbid anxiety disorder, for which specific treatments may be indicated.

Mixed anxiety and depression — Mixed anxiety and depression (MAD) has been defined in the International Classification of Diseases, 10th Revision (ICD-10) as a condition where the symptoms of both anxiety and depression are present for at least one month, with neither being clearly predominant nor sufficient to meet diagnostic criteria for either an anxiety or a depressive disorder [61]. ICD-10 does not provide additional criteria for diagnosing the disorder. Proposed criteria appeared in the appendix of DSM-IV-TR as a disorder in need of further study. MAD was not included in DSM-5, owing to the fact that systematic review of research failed to support its existence.

Differential diagnosis — The differential diagnoses of individual anxiety disorders and depressive disorders are described separately.

(See "Unipolar depression in adults: Epidemiology".)

(See "Unipolar depression in adults: Assessment and diagnosis".)

(See "Unipolar depression in adults: Course of illness".)

(See "Generalized anxiety disorder in adults: Epidemiology, pathogenesis, clinical manifestations, course, assessment, and diagnosis".)

(See "Social anxiety disorder in adults: Epidemiology, clinical features, assessment, and diagnosis".)

(See "Obsessive-compulsive disorder in adults: Epidemiology, clinical features, and diagnosis".)

(See "Panic disorder in adults: Epidemiology, clinical manifestations, and diagnosis".)

(See "Agoraphobia in adults: Epidemiology, pathogenesis, clinical manifestations, course, and diagnosis".)

A table distinguishes among symptoms shared by depression and GAD, symptoms specific to depression, and symptoms specific to GAD (table 2).

Diagnostic reliability — Given the overlap in DSM diagnostic criteria for depression and anxiety disorders, the accuracy of diagnosis of these disorders has been questioned, and study findings have been mixed:

A study of clinical diagnosis in 362 outpatients found good to excellent inter-rater reliability for the disorders [62]. Structured interviews were conducted by clinical psychologists and advanced graduate students.

A cross-sectional study found evidence of poor diagnostic accuracy in clinical samples of 666 patients with “pure” GAD, 772 “pure” with a major depressive episode, and 278 with co-occurring GAD and major depression [63]. Primary care clinicians made accurate diagnoses in only 34 percent of patients with GAD and 64 percent of patients with a major depressive episode.

Rating scales — Scales that have demonstrated good reliability and validity in the assessment of anxiety and depression, either presenting individually or co-occurring, include the following:

Depression and anxiety – The Depression and Anxiety Stress Scale (DASS) is potentially the most useful instrument for the assessment of patients with co-occurring depression and GAD symptoms, or when discrimination among mixed anxiety and depressive symptoms is unclear [64]. DASS has been shown to be reliable, accurate in its assessment of global anxiety, and able to separate anxiety and depressive symptoms.

Depression – The Montgomery Asberg Depression Rating Scale has been shown to be superior to other clinician-administered instruments, best capturing symptoms of depression [65]. It has demonstrated excellent discrimination between depressed and non-depressed individuals [66], and between self-assessed depression and personality disorders [67]. It has also demonstrated good reliability and validity in older adult populations [68].

Generalized anxiety – The Hamilton Rating Scale for Anxiety (HAMA) is the gold standard measure for the assessment of GAD symptom severity. This scale is reliable and valid, particularly when used with a structured interview guide [69]. The HAMA has demonstrated good ability to discriminate between anxiety and depression [70].

OCD – The Yale Brown Obsessive Compulsive Scale (YBOCS) has shown good discrimination between OCD and depression as well as other anxiety disorders in initial validation study, and good sensitivity to change [71,72]. The self-report adaptation of the 10-item YBOCS scale and symptom checklist has shown similar reliability patterns [73].

Panic disorder – The most commonly used observer-rated scale for panic disorder is the seven-item Panic Disorder Severity Scale (PDSS), which has demonstrated good inter-rater reliability and internal consistency with favorable validity and sensitivity to change when compared to diagnostic interview [74,75].

PTSD – The Clinician Administered PTSD Scale (CAPS) has emerged as the most widely used instrument in clinical trials and has proven to be both an effective assessment tool and severity measure, despite substantial correlation with other measures of depression and anxiety [76].

Despite their wide use, the State Trait Anxiety Inventory and the Hamilton Rating Scale for Depression have been criticized for an inability to distinguish between anxious and depressive symptoms [77-80].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Anxiety and anxiety disorders in adults".)

SUMMARY AND RECOMMENDATIONS

Comorbid mood and anxiety disorders – Population-based studies conducted in several countries have shown high rates of co-occurrence between anxiety disorders and mood disorders. Mood disorders have shown the highest correlations with generalized anxiety disorder (GAD) and the lowest with agoraphobia and specific phobias (table 1). (See 'Epidemiology' above.)

Risk factors – Research has found that patients with co-occurring anxiety and mood disorders are more likely to be female, younger (25 to 34 years), have a lower education level, live alone, be unemployed, have a parental psychiatric history, and to have experienced childhood trauma than those with purely an anxiety or mood disorder. (See 'Risk factors' above.)

Pathogenesis While our understanding of the etiology of co-occurring anxiety and depression is limited, research has identified similarities between the two disorders in their neurobiology, genetic structure, and presence of neuroticism and harm avoidance. (See 'Pathogenesis' above.)

Clinical manifestations – Co-occurring GAD and depression can present on a continuum, from principally anxiety symptoms to mixed anxiety and depression, to principally depressive symptoms. Symptoms commonly present in either disorder include irritability, agitation/restlessness, difficulties concentrating, insomnia, and fatigue (table 2). (See 'Clinical manifestations' above.)

Course – Co-occurring anxiety and depressive disorders have been found to differ from the individual disorder categories in age of onset, life course, and treatment outcome. Presence of both disorders together significantly decreases the odds of recovery, increases the time to therapeutic onset for pharmacotherapy, and is associated with a more chronic course. (See 'Course' above.)

Assessment and diagnosis – Our diagnostic assessment for potentially co-occurring anxiety and depressive disorders includes a careful history and complete physical examination. We screen for stressful life events, family psychiatric history, social history, history of substance use and history of past sexual, physical, or emotional abuse.

  1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), American Psychiatric Association, 2013.
  2. Kessler RC, Berglund P, Demler O, et al. Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry 2005; 62:593.
  3. Kessler RC, Birnbaum HG, Shahly V, et al. Age differences in the prevalence and co-morbidity of DSM-IV major depressive episodes: results from the WHO World Mental Health Survey Initiative. Depress Anxiety 2010; 27:351.
  4. Alonso J, Lépine JP, ESEMeD/MHEDEA 2000 Scientific Committee. Overview of key data from the European Study of the Epidemiology of Mental Disorders (ESEMeD). J Clin Psychiatry 2007; 68 Suppl 2:3.
  5. Lamers F, van Oppen P, Comijs HC, et al. Comorbidity patterns of anxiety and depressive disorders in a large cohort study: the Netherlands Study of Depression and Anxiety (NESDA). J Clin Psychiatry 2011; 72:341.
  6. Johansson R, Carlbring P, Heedman Å, et al. Depression, anxiety and their comorbidity in the Swedish general population: point prevalence and the effect on health-related quality of life. PeerJ 2013; 1:e98.
  7. Kessler RC, Sampson NA, Berglund P, et al. Anxious and non-anxious major depressive disorder in the World Health Organization World Mental Health Surveys. Epidemiol Psychiatr Sci 2015; 24:210.
  8. Cyranowski JM, Schott LL, Kravitz HM, et al. Psychosocial features associated with lifetime comorbidity of major depression and anxiety disorders among a community sample of mid-life women: the SWAN mental health study. Depress Anxiety 2012; 29:1050.
  9. Braam AW, Copeland JR, Delespaul PA, et al. Depression, subthreshold depression and comorbid anxiety symptoms in older Europeans: results from the EURODEP concerted action. J Affect Disord 2014; 155:266.
  10. Almeida OP, Draper B, Pirkis J, et al. Anxiety, depression, and comorbid anxiety and depression: risk factors and outcome over two years. Int Psychogeriatr 2012; 24:1622.
  11. Adams GC, Balbuena L, Meng X, Asmundson GJ. When social anxiety and depression go together: A population study of comorbidity and associated consequences. J Affect Disord 2016; 206:48.
  12. de Graaf R, Bijl RV, Smit F, et al. Risk factors for 12-month comorbidity of mood, anxiety, and substance use disorders: findings from the Netherlands Mental Health Survey and Incidence Study. Am J Psychiatry 2002; 159:620.
  13. Sanderson WC, Barlow DH. A description of patients diagnosed with DSM-III-R generalized anxiety disorder. J Nerv Ment Dis 1990; 178:588.
  14. Tükel R, Meteris H, Koyuncu A, et al. The clinical impact of mood disorder comorbidity on obsessive-compulsive disorder. Eur Arch Psychiatry Clin Neurosci 2006; 256:240.
  15. Brown TA, Barlow DH. Comorbidity among anxiety disorders: implications for treatment and DSM-IV. J Consult Clin Psychol 1992; 60:835.
  16. Brown TA, Campbell LA, Lehman CL, et al. Current and lifetime comorbidity of the DSM-IV anxiety and mood disorders in a large clinical sample. J Abnorm Psychol 2001; 110:585.
  17. Nam YY, Kim CH, Roh D. Comorbid panic disorder as an independent risk factor for suicide attempts in depressed outpatients. Compr Psychiatry 2016; 67:13.
  18. Zhou Y, Cao Z, Yang M, et al. Comorbid generalized anxiety disorder and its association with quality of life in patients with major depressive disorder. Sci Rep 2017; 7:40511.
  19. Pini S, Cassano GB, Simonini E, et al. Prevalence of anxiety disorders comorbidity in bipolar depression, unipolar depression and dysthymia. J Affect Disord 1997; 42:145.
  20. Rodney J, Prior N, Cooper B, et al. The comorbidity of anxiety and depression. Aust N Z J Psychiatry 1997; 31:700.
  21. Fava M, Rankin MA, Wright EC, et al. Anxiety disorders in major depression. Compr Psychiatry 2000; 41:97.
  22. Verhagen M, van der Meij A, Franke B, et al. Familiality of major depressive disorder and patterns of lifetime comorbidity. The NEMESIS and GenMood studies. A comparison of three samples. Eur Arch Psychiatry Clin Neurosci 2008; 258:505.
  23. Wittchen HU, Kessler RC, Pfister H, Lieb M. Why do people with anxiety disorders become depressed? A prospective-longitudinal community study. Acta Psychiatr Scand Suppl 2000; :14.
  24. Bittner A, Goodwin RD, Wittchen HU, et al. What characteristics of primary anxiety disorders predict subsequent major depressive disorder? J Clin Psychiatry 2004; 65:618.
  25. van der Veen DC, van Zelst WH, Schoevers RA, et al. Comorbid anxiety disorders in late-life depression: results of a cohort study. Int Psychogeriatr 2015; 27:1157.
  26. Schuch JJ, Roest AM, Nolen WA, et al. Gender differences in major depressive disorder: results from the Netherlands study of depression and anxiety. J Affect Disord 2014; 156:156.
  27. Pannekoek JN, van der Werff SJ, van Tol MJ, et al. Investigating distinct and common abnormalities of resting-state functional connectivity in depression, anxiety, and their comorbid states. Eur Neuropsychopharmacol 2015; 25:1933.
  28. Damsa C, Kosel M, Moussally J. Current status of brain imaging in anxiety disorders. Curr Opin Psychiatry 2009; 22:96.
  29. Etkin A, Wager TD. Functional neuroimaging of anxiety: a meta-analysis of emotional processing in PTSD, social anxiety disorder, and specific phobia. Am J Psychiatry 2007; 164:1476.
  30. Martin EI, Ressler KJ, Binder E, Nemeroff CB. The neurobiology of anxiety disorders: brain imaging, genetics, and psychoneuroendocrinology. Psychiatr Clin North Am 2009; 32:549.
  31. Li Y, Wang W, Liu T, et al. Source analysis of P3a and P3b components to investigate interaction of depression and anxiety in attentional systems. Sci Rep 2015; 5:17138.
  32. Liu JJ, Galfalvy HC, Cooper TB, et al. Omega-3 polyunsaturated fatty acid (PUFA) status in major depressive disorder with comorbid anxiety disorders. J Clin Psychiatry 2013; 74:732.
  33. de Graaf R, Bijl RV, ten Have M, et al. Rapid onset of comorbidity of common mental disorders: findings from the Netherlands Mental Health Survey and Incidence Study (NEMESIS). Acta Psychiatr Scand 2004; 109:55.
  34. Khan AA, Jacobson KC, Gardner CO, et al. Personality and comorbidity of common psychiatric disorders. Br J Psychiatry 2005; 186:190.
  35. Enoch MA, White KV, Waheed J, Goldman D. Neurophysiological and genetic distinctions between pure and comorbid anxiety disorders. Depress Anxiety 2008; 25:383.
  36. Kendler KS, Prescott CA, Myers J, Neale MC. The structure of genetic and environmental risk factors for common psychiatric and substance use disorders in men and women. Arch Gen Psychiatry 2003; 60:929.
  37. Hettema JM, Prescott CA, Myers JM, et al. The structure of genetic and environmental risk factors for anxiety disorders in men and women. Arch Gen Psychiatry 2005; 62:182.
  38. Middeldorp CM, Cath DC, Van Dyck R, Boomsma DI. The co-morbidity of anxiety and depression in the perspective of genetic epidemiology. A review of twin and family studies. Psychol Med 2005; 35:611.
  39. Minelli A, Maffioletti E, Cloninger CR, et al. Role of allelic variants of FK506-binding protein 51 (FKBP5) gene in the development of anxiety disorders. Depress Anxiety 2013; 30:1170.
  40. Kenna HA, Tartter M, Hall SS, et al. High rates of comorbid depressive and anxiety disorders among women with premutation of the FMR1 gene. Am J Med Genet B Neuropsychiatr Genet 2013; 162B:872.
  41. Clark LA, Watson D. Tripartite model of anxiety and depression: psychometric evidence and taxonomic implications. J Abnorm Psychol 1991; 100:316.
  42. Clark DA, Beck AT, Beck JS. Symptom differences in major depression, dysthymia, panic disorder, and generalized anxiety disorder. Am J Psychiatry 1994; 151:205.
  43. Barlow DH, DiNardo PA, Vermilyea BB, et al. Co-morbidity and depression among the anxiety disorders. Issues in diagnosis and classification. J Nerv Ment Dis 1986; 174:63.
  44. Kendall PC, Watson D. Anxiety and Depression: distinctive and overlapping features, Academic Press, San Diego, CA 1989.
  45. Beesdo K, Pine DS, Lieb R, Wittchen HU. Incidence and risk patterns of anxiety and depressive disorders and categorization of generalized anxiety disorder. Arch Gen Psychiatry 2010; 67:47.
  46. Bruce SE, Yonkers KA, Otto MW, et al. Influence of psychiatric comorbidity on recovery and recurrence in generalized anxiety disorder, social phobia, and panic disorder: a 12-year prospective study. Am J Psychiatry 2005; 162:1179.
  47. Kessler RC, Gruber M, Hettema JM, et al. Co-morbid major depression and generalized anxiety disorders in the National Comorbidity Survey follow-up. Psychol Med 2008; 38:365.
  48. Meier SM, Petersen L, Mattheisen M, et al. Secondary depression in severe anxiety disorders: a population-based cohort study in Denmark. Lancet Psychiatry 2015; 2:515.
  49. Hofmeijer-Sevink MK, Batelaan NM, van Megen HJ, et al. Clinical relevance of comorbidity in anxiety disorders: a report from the Netherlands Study of Depression and Anxiety (NESDA). J Affect Disord 2012; 137:106.
  50. Grant BF, Hasin DS, Stinson FS, et al. Prevalence, correlates, co-morbidity, and comparative disability of DSM-IV generalized anxiety disorder in the USA: results from the National Epidemiologic Survey on Alcohol and Related Conditions. Psychol Med 2005; 35:1747.
  51. Merikangas KR, Zhang H, Avenevoli S, et al. Longitudinal trajectories of depression and anxiety in a prospective community study: the Zurich Cohort Study. Arch Gen Psychiatry 2003; 60:993.
  52. Rush AJ, Trivedi MH, Wisniewski SR, et al. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry 2006; 163:1905.
  53. Farabaugh A, Alpert J, Wisniewski SR, et al. Cognitive therapy for anxious depression in STAR(*) D: what have we learned? J Affect Disord 2012; 142:213.
  54. Fava M, Rush AJ, Alpert JE, et al. Difference in treatment outcome in outpatients with anxious versus nonanxious depression: a STAR*D report. Am J Psychiatry 2008; 165:342.
  55. Stein DJ, Baldwin DS, Baldinetti F, Mandel F. Efficacy of pregabalin in depressive symptoms associated with generalized anxiety disorder: a pooled analysis of 6 studies. Eur Neuropsychopharmacol 2008; 18:422.
  56. Overbeek T, Schruers K, Vermetten E, Griez E. Comorbidity of obsessive-compulsive disorder and depression: prevalence, symptom severity, and treatment effect. J Clin Psychiatry 2002; 63:1106.
  57. Woody S, McLean PD, Taylor S, Koch WJ. Treatment of major depression in the context of panic disorder. J Affect Disord 1999; 53:163.
  58. Rief W, Trenkamp S, Auer C, Fichter MM. Cognitive behavior therapy in panic disorder and comorbid major depression. A naturalistic study. Psychother Psychosom 2000; 69:70.
  59. Ledley DR, Huppert JD, Foa EB, et al. Impact of depressive symptoms on the treatment of generalized social anxiety disorder. Depress Anxiety 2005; 22:161.
  60. Fava M, Alpert JE, Carmin CN, et al. Clinical correlates and symptom patterns of anxious depression among patients with major depressive disorder in STAR*D. Psychol Med 2004; 34:1299.
  61. World Health Organization. International Classification of Diseases and Related Health Conditions (10th Revision), World Health Organization, Geneva, Switzerland 1992.
  62. Brown TA, Di Nardo PA, Lehman CL, Campbell LA. Reliability of DSM-IV anxiety and mood disorders: implications for the classification of emotional disorders. J Abnorm Psychol 2001; 110:49.
  63. Wittchen HU, Kessler RC, Beesdo K, et al. Generalized anxiety and depression in primary care: prevalence, recognition, and management. J Clin Psychiatry 2002; 63 Suppl 8:24.
  64. Antony MM, Bieling PJ, Cox BJ, et al. Psychometric properties of the 42-item and 21-item versions of the Depression Anxiety Stress Scales in clinical groups and a community sample. Psychol Assess 1998; 10:176.
  65. Furukawa TA. Assessment of mood: guides for clinicians. J Psychosom Res 2010; 68:581.
  66. Bernstein IH, Rush AJ, Stegman D, et al. A Comparison of the QIDS-C16, QIDS-SR16, and the MADRS in an Adult Outpatient Clinical Sample. CNS Spectr 2010; 15:458.
  67. Svanborg P, Asberg M. A comparison between the Beck Depression Inventory (BDI) and the self-rating version of the Montgomery Asberg Depression Rating Scale (MADRS). J Affect Disord 2001; 64:203.
  68. Mottram P, Wilson K, Copeland J. Validation of the Hamilton Depression Rating Scale and Montgommery and Asberg Rating Scales in terms of AGECAT depression cases. Int J Geriatr Psychiatry 2000; 15:1113.
  69. Shear MK, Vander Bilt J, Rucci P, et al. Reliability and validity of a structured interview guide for the Hamilton Anxiety Rating Scale (SIGH-A). Depress Anxiety 2001; 13:166.
  70. Vaccarino AL, Evans KR, Sills TL, Kalali AH. Symptoms of anxiety in depression: assessment of item performance of the Hamilton Anxiety Rating Scale in patients with depression. Depress Anxiety 2008; 25:1006.
  71. Goodman WK, Price LH, Rasmussen SA, et al. The Yale-Brown Obsessive Compulsive Scale. I. Development, use, and reliability. Arch Gen Psychiatry 1989; 46:1006.
  72. Gibb BE, Coles ME, Heimberg RG. Differentiating symptoms of social anxiety and depression in adults with social anxiety disorder. J Behav Ther Exp Psychiatry 2005; 36:99.
  73. Steketee G, Frost R, Bogart K. The Yale-Brown Obsessive Compulsive Scale: interview versus self-report. Behav Res Ther 1996; 34:675.
  74. Shear MK, Brown TA, Barlow DH, et al. Multicenter collaborative panic disorder severity scale. Am J Psychiatry 1997; 154:1571.
  75. Shear MK, Rucci P, Williams J, et al. Reliability and validity of the Panic Disorder Severity Scale: replication and extension. J Psychiatr Res 2001; 35:293.
  76. Weathers FW, Keane TM, Davidson JR. Clinician-administered PTSD scale: a review of the first ten years of research. Depress Anxiety 2001; 13:132.
  77. Kennedy BL, Schwab JJ, Morris RL, Beldia G. Assessment of state and trait anxiety in subjects with anxiety and depressive disorders. Psychiatr Q 2001; 72:263.
  78. Creamer M, Foran J, Bell R. The Beck Anxiety Inventory in a non-clinical sample. Behav Res Ther 1995; 33:477.
  79. Bagby RM, Ryder AG, Schuller DR, Marshall MB. The Hamilton Depression Rating Scale: has the gold standard become a lead weight? Am J Psychiatry 2004; 161:2163.
  80. Demyttenaere K, De Fruyt J. Getting what you ask for: on the selectivity of depression rating scales. Psychother Psychosom 2003; 72:61.
Topic 14623 Version 21.0

References

آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟