ارتباط بین افسردگی آتیپیک و اختلال اضطراب اجتماعی

In this study, we aimed to investigate the effects of atypical and non-atypical depression comorbidity on the clinical characteristics and course of social anxiety disorder (SAD). A total of 247 patients with SAD were enrolled: 145 patients with a current depressive episode (unipolar or bipolar) with atypical features, 43 patients with a current depressive episode with non-atypical features and 25 patients without a lifetime history of depressive episodes were compared regarding sociodemographic and clinical features, comorbidity rates, and severity of SAD, depression and functional impairment. Thirty four patients with a past but not current history of major depressive episodes were excluded from the comparisons. 77.1% of current depressive episodes were associated with atypical features. Age at onset of SAD and age at initial major depressive episode were lower in the group with atypical depression than in the group with non-atypical depression. History of suicide attempts and bipolar disorder comorbidity was more common in the atypical depression group as well. Atypical depression group has higher SAD and depression severity and lower functionality than group with non-atypical depression. Our results indicate that the presence of atypical depression is associated with more severe symptoms and more impairment in functioning in patients with SAD.

Social anxiety disorder (SAD) is common in the general population with a lifetime prevalence of 10–15% and a 1-year prevalence of 5–10% (Kessler et al., 1994, Kessler et al., 2005, Stein, 2006, Acarturk et al., 2008 and Ohayon and Schatzberg, 2010). SAD and major depressive disorder (MDD) are closely associated with each other; the frequency of comorbid MDD in patients with SAD is reported to be between 35% and 74.5% (Stein et al., 1990, Van Ameringen et al., 1991, Perugi et al., 1999, Perugi et al., 2001 and Koyuncu et al., 2014) whereas the frequency of comorbid SAD in patients with MDD is reported to be approximately 20–30% (Alpert et al., 1997, Kessler et al., 1999, Brown et al., 2001 and Rush et al., 2005). Furthermore, SAD was found to be a predictor for the subsequent development of MDD (Weiller et al., 1996, Kessler et al., 1999, Stein et al., 2001, Bittner et al., 2004, Beesdo et al., 2007 and Ohayon and Schatzberg, 2010). In addition, SAD was found to be associated with severity and persistence of comorbid mood disorders (Kessler et al., 1999 and Stein et al., 2001). Atypical depression was defined as a subgroup of MDD in DSM-IV (American Psychiatric Association: APA, 1994). According to the DSM-IV, the main criterion of atypical depression is the presence of mood reactivity in combination with at least two of four secondary criteria (hypersomnia, increased appetite or weight gain, leaden paralysis, and interpersonal rejection sensitivity). In community samples, it was suggested that 15–29% of patients with MDD had atypical depression and this rate corresponded to a 1-year prevalence of approximately 1–4% in the community (Thase, 2007). Considerably similar estimates were reported in the studies performed with clinical samples: atypical depression was encountered in 18–36% of patients with MDD (Thase, 2007). It was reported that female gender was more common in patients with atypical MD episodes compared to patients with non-atypical MD episodes (Thase et al., 1991 and Asnis et al., 1995; Benazzi, 1999a, 1999b; Agosti and Stewart, 2001, Angst et al., 2002, Posternak and Zimmerman, 2002a, Matza et al., 2003, Novick et al., 2005, Thase, 2007, Thase, 2009 and Blanco et al., 2012). Overall, patients with atypical depression have an earlier age of onset compared to the patients with non-atypical depression (Thase et al., 1991 and Horwath et al., 1992; Benazzi, 1999b; Angst et al., 2002, Posternak and Zimmerman, 2002a, Matza et al., 2003, Novick et al., 2005, Thase, 2007, Thase, 2009 and Blanco et al., 2012). In addition to these, it was reported that depression with atypical features is associated with longer disease duration (Thase et al., 1991, Angst et al., 2002 and Posternak and Zimmerman, 2002a), more depressive recurrences (Horwath et al., 1992 and Blanco et al., 2012), more chronic disease course (McGinn et al., 1996; Benazzi, 1999b; Posternak and Zimmerman, 2002a, Angst et al., 2002, Thase, 2007, Thase, 2009 and Stewart et al., 2009), more suicidality (Horwath et al., 1992, Matza et al., 2003 and Blanco et al., 2012) and more severe symptoms (Novick et al., 2005, Thase, 2009 and Blanco et al., 2012). The presence of atypical depression was found to be associated with the presence of more comorbid diagnoses (Alpert et al., 1997, Novick et al., 2005, Thase, 2009 and Blanco et al., 2012). There are also studies reporting that atypical depression is associated with SAD as a highly comorbid condition (Perugi et al., 1998, Sullivan et al., 1998, Parker et al., 2002, Angst et al., 2002, Matza et al., 2003 and Blanco et al., 2012). Posternak and Zimmerman (2002a) have reported that SAD comorbidity in atypical MD group was significantly higher than in non-atypical MD group. Although many studies have found an association between SAD and atypical depression, it must be acknowledged that these findings are nor unequivocal. For example, in a pharmacological trial, Schneier et al. (2003) found atypical depression in only three patients (14.3%), although 18 (85.7%) fulfilled the criterion for interpersonal rejection sensitivity. They concluded that the overlap of social anxiety disorder with atypical features of depression may primarily be due to the shared feature of rejection sensitivity. Additionally, in a study performed with 129 SAD patients, the group with generalized SAD had higher rates of atypical depression than the group with non-generalized SAD (Mannuzza et al., 1995). In another study performed with adult patients with MDD, atypical depression was significantly higher in the group with SAD+avoidant personality disorder compared to the group with SAD without avoidant personality disorder (Alpert et al., 1997). This association between atypical MD and SAD might be related to the common features which have a role in both disorders. Interpersonal rejection sensitivity is defined as a cognitive–affective processing disposition to anxiously expect, readily perceive and overreact to social rejection (Feldman and Downey, 1994). Interpersonal rejection sensitivity is seen as a common feature of both SAD (Liebowitz et al., 1985) and depression with atypical features (APA, 1994). This feature may represent an underlying personality trait of individuals with SAD and especially with the generalized subtype of SAD (Harb et al., 2002). In atypical depression, the primacy of mood reactivity in relation to the other diagnostic criteria has been questioned and reformulated definitions of atypical depression arguing for the primacy of rejection sensitivity as against mood reactivity have been suggested (Parker, 2007). Although it was reported that when major depression existed in the presence of a comorbid anxiety disorder, the likelihood of presenting with atypical features doubled (Posternak and Zimmerman, 2002b), this common feature of atypical depression and SAD helps explaining the question of why to study SAD specifically with atypical depression, rather than anxiety disorders more generally. To the best of our knowledge, there is no study in SAD patients investigating the effects of comorbid atypical depression or non-atypical depression on clinical characteristics of SAD in detail. In this study, our aim is to investigate the effects of the presence of major depression (unipolar or bipolar) with or without current atypical features on the clinical characteristics of SAD. It would be important to know about any differences in clinical characteristics between SAD patients with atypical versus non-atypical depression also because of possible treatment implications. For example, interpersonal rejection sensitivity may be a focus for psychotherapy in SAD patients with atypical depression. Additionally, there are reports of differential response to different classes of antidepressant medications in treating subgroups of patients with MDD with atypical features (Zisook et al., 1985 and Quitkin et al., 1991). Therefore, such discrimination may provide information to guide selecting an effective antidepressant medication for the patients according to their comorbidity profile.

Eighty-five (34.4%) of 247 patients were females and 162 (65.6%) of them were males. Fifty-five patients (22.3%) were married, 185 patients (74.9%) were single and seven patients (2.8%) were divorced. Mean age of the patients was 27.61 years (S.D.: 6.22), mean of total years spent in education was 12.89 years (S.D.: 2.84), mean age of onset of SAD was 13.64 years (S.D.: 5.61) and mean age of first MD episode was 17.61 years (S.D.: 5.12). There was a history of psychiatric treatment in 128 (51.8%) of the patients. One hundred nineteen patients (48.2%) had never received psychiatric treatment. There was at least one suicidal attempt history in 15 (6.1%) of the patients. No statistically significant difference was determined between the three groups with regard to sociodemographical variables such as gender distribution, mean age, educational level and marital status (Table 1). Also, no significant difference was found between the groups regarding history of psychiatric treatment. Table 1. Comparison of sociodemographical and clinical characteristics of atypical MD, non-atypical MD and non-MD groups. Sociodemographical and clinical characteristics Atypical MD(n=145) Non-atypical MD(n=43) Non-MD(n=25) Chi-square p Marital status—married 28 (19.3%) 7 (16.3%) 9 (36.0%) 5.00 0.304 Gender—female 54 (37.2%) 13 (30.2%) 5 (20.0%) 3.14 0.208 Suicidal attempt (%) 15 (10.3%) 0 0 7.56 0.017 Mean (S.D.) Mean (S.D.) Mean (S.D.) F p Mean age 27.0 (6.3) 27.1 (5.1) 29.8 (6.1) 2.32 0.100 Mean educational level (years) 12.6 (2.7) 12.6 (3.2) 13.7 (2.7) 1.41 0.247 Mean age of onset of SAD 12.8 (5.6) 15.2 (5.0) 14.4 (6.5) 3.57 0.030 Mean age of first treatment contact 24.3 (5.9) 25.1 (4.6) 29.5 (6.1) 8.54 <0.001 Mean age of first MD episode 18.1 (4.9) 20.5 (5.7) N/A 7.62 0.006 Number of lifetime comorbidities 1.7 (0.9) 1.5 (0.6) 0.0 (0.0) 48.59 <0.001 Number of lifetime total depressive episodes 5.9 (3.8) 3.4 (2.4) N/A 37.68 <0.001 Table options The mean age of onset of SAD in atypical MD group was lower than in non-atypical MD group. There was no difference between the other groups in terms of age at SAD onset. Mean age of first depressive episode in atypical MD group was also lower than in non-atypical MD group. Patients in both atypical and non-atypical MD groups had their first treatment contact at an earlier age than the patients in non-MD group. Compared to the non-atypical MD group, atypical MD group had a higher mean number of total depressive episodes and also higher rates of suicidal attempt history (Table 1). There was no difference between the two MD groups in terms of number of comorbid diagnoses while they both had higher numbers of lifetime psychiatric comorbid diagnoses than the non-MD group (Table 1). Psychiatric comorbidity profiles of the groups are presented in Table 2. Three significant findings are as follows: 1) bipolar disorder comorbidity in atypical MD group was more frequent than in the other two groups, 2) OCD in atypical MD group was higher than in non-MD group and 3) specific phobia was more frequent in both atypical MD and non-atypical MD groups than in non-MD group. Table 2. Rates of lifetime comorbidities in atypical MD, non-atypical MD and non-MD groups. Comorbid diagnosis Atypical MD (n=145) Non-atypical MD (n=43) Non-MD (n=25) Chi-square p Bipolar disorder 37 (25.5%) 1 (2.3%) 0 (0%) 18.32 <0.001 PD 12 (8.3%) 1 (2.3%) 0 (0.0%) 3.89 0.200 OCD 21 (14.5%) 2 (4.7%) 0 (0%) 6.75 0.032 SP 16 (17.3%) 6 (15.8%) 0 (0%) 5.11 0.045 PTSD 9 (6.2%) 1 (2.3%) 0 (0%) 2.51 0.392 Alcohol–substance use disorder 14 (9.7%) 3 (7.0%) 0 (0.0%) 2.78 0.354 PD: panic disorder, OCD: obsessive compulsive disorder, GAD: generalized anxiety disorder, SP: specific phobia, PTSD: post-traumatic stress disorder. Table options Mean LSAS anxiety, avoidance and total scores of atypical MD group were significantly higher than both of non-atypical MD and non-MD groups. However, there was no difference between non-atypical MD and non-MD groups. Apart from higher SAD severity, the atypical MD group was also associated with more impairment in functionality: the mean scores of current GAF and GAF in the past year were significantly lower in the atypical MD group compared to the other two groups. Additionally, GAF scores of non-atypical MD group were lower than those of non-MD group. As it was expected, mean BDI scores of both atypical MD and non-atypical MD groups were significantly higher than those of non-MD group. Furthermore, mean BDI scores in atypical MD group was also higher than in non-atypical MD group (Table 3). Table 3. Comparison of atypical MD, non-atypical MD and non-MD groups in terms of rating scales scores. The rating scales Atypical MD(n=145) Mean (S.D.) Non-atypical MD(n=43) Mean (S.D.) Non-MD(n=25) Mean (S.D.) F p LSAS-fear 71.6 (11.5) 63.0 (13.2) 62.0 (14.9) 12.27 <0.001 LSAS-avoidance 68.5 (11.2) 60.4 (14.1) 59.4 (16.5) 10.56 <0.001 LSAS-total 140.0 (22.0) 123.4 (26.4) 121.0 (30.8) 12.24 <0.001 GAF-current 59.8 (6.9) 65.2 (8.3) 74.2 (4.9) 48.62 <0.001 GAF-past year 62.1 (7.5) 67.5 (8.6) 75.0 (4.3) 35.17 <0.001 BDI 25.2 (8.6) 17.1 (5.7) 5.1 (3.9) 80.05 <0.001 LSAS: Liebowitz Social Anxiety Scale; GAF: Global Assessment of Functioning, BDI: Beck Depression Inventory. Table options Since the differences found on symptom severity and functional status might have been due to the fact that bipolar disorder was significantly more present in the atypical depression group, we repeated the analyses on severity and functioning excluding patients with bipolar disorder (37 patients from the atypical depression group and one patient from the non-atypical depression group have been excluded). One hundred eight patients remaining in the atypical group were compared with 42 patients from the non-atypical group and it was found that all severity and functioning scores remained significantly different between the two groups: atypical depression was associated with higher scores in LSAS anxiety, avoidance, total (p<0.001, p=0.001, p<0.001, respectively) and BDI scores (p<0.001) and lower GAF scores (p=0.001 for current and p<0.001 for last year) compared to non-atypical depression. However, suicide attempt rates were no longer significantly different between the two groups after the exclusion of patients with bipolar disorder.