همبودی اختلال اضطراب اجتماعی در بیماران مبتلا به اختلال دو قطبی: تکرار بالینی

Abstract Background The authors investigated frequency, clinical correlates and onset temporal relationship of social anxiety disorder (SAD) in adult patients with a diagnosis of bipolar I disorder. Methods Subjects were 189 patients whose diagnoses were assessed by the Structured Clinical Interview for DSM-III-R—Patient Version. Results Twenty-four patients (12.7%) met DSM-III-R criteria for lifetime SAD; of these, 19 (10.1% of entire sample) had SAD within the last month. Significantly more bipolar patients with comorbid SAD also had substance use disorders compared to those without. On the HSCL-90, levels of interpersonal sensitivity, obsessiveness, phobic anxiety and paranoid ideation were significantly higher in bipolar patients with SAD than in those without. Bipolar patients with comorbid SAD recalled separation anxiety problems (school refusal) more frequently during childhood than those without. Lifetime SAD comorbidity was associated with an earlier age at onset of syndromal bipolar disorder. Pre-existing OCD tended to delay the onset of bipolarity. Conclusions Social anxiety disorder comorbidity is not rare among patients with bipolar disorder and is likely to affect age of onset and phenomenology of bipolar disorder. These findings may influence treatment planning and the possibility of discovering a pathophysiological relationship between SAD and bipolarity.

Introduction Data from the US National Comorbidity Survey (NCS) evidenced a strong association between lifetime social anxiety disorder (SAD) and bipolar I disorder (odds ratio 5.9) (Kessler, Stang, Wittchen, Stein, & Walters, 1999). In addition, the time-lagged effects of temporally primary SAD predicted subsequent onset of bipolar disorder with an odds ratio (OR) of 2.6 (Kessler et al., 1999). The Hungarian National Epidemiologic Survey observed 7.8% of persons with bipolar disorder plus lifetime SAD (Szadoczky, Papp, Vitrai, Rihmer, & Fiirdei, 1998). In clinical settings, Cassano, Pini, Saettoni, and Dell’Osso (1999) investigated 77 inpatients with bipolar I or schizoaffective disorder and found SAD present in 8.2% (N = 14) of the sample. Bipolar I outpatients strictly defined as remitted (N = 129) had an overall rate of psychiatric comorbidity of 31%, but only 1.6% also had SAD ( Vieta et al., 2001). McElroy et al. (2001) reported on 288 patients with bipolar I or II disorder: among the 239 outpatients with bipolar I disorder, lifetime rate of SAD was17% and among the 49 bipolar II the lifetime rate was 12%. In a sample of 318 bipolar I patients, Henry et al. (2003) found an 11% of phobia (including agoraphobia without panic disorder, social phobia and other specific phobias). More recently, Simon et al. (2004) examined anxiety comorbidity and its correlates in a cross-sectional sample from the first 500 patients with bipolar I or bipolar II disorder enrolled in the Systematic Treatment Enhancement Program for Bipolar Disorder. Of the 360 subjects with bipolar I disorder, 23.2% fulfilled a DSM-IV diagnosis of social anxiety disorder. These last four studies were carried out in large clinical populations. However, none of these studies examined the impact of SAD on bipolar disorder. Mick, Biederman, Faraone, Murray, and Wozniak (2003) examined the effect of age at onset of bipolar disorder in a sample of 44 non-referred adults and found that an earlier age at onset of bipolar disorder predicted a higher risk for anxiety disorders, suggesting that age at onset of bipolar disorder was a modifier of the risk for anxiety disorders in bipolar subjects. Perlis et al. (2004) found that social phobia was significantly associated with early-onset bipolar disorder. In particular, they found a significantly greater likelihood of association in the <13 years bipolar onset group (31.2%, OR = 2.8) and in the 13–18 years bipolar onset group (23.4%, OR = 2.0) respect to the >18 years bipolar onset group (13.3%). The present study explores the frequency and correlates of SAD comorbidity in a sample of 189 patients with a principal diagnosis of bipolar I disorder. In addition, we explore the temporal relationship between onset of SAD and of bipolar disorder.

4. Results Of the 189 patients, 166 had bipolar I disorder and 23 had schizoaffective disorder, bipolar type. Mean age was 33.5 years (S.D. ± 10.3); 57.1% were women, 48.1% were in their first hospitalization; there were no significant differences between the two diagnostic groups on these variables. Scores on the SUMD at the time of the evaluation did not differ significantly between the two diagnostic subgroups. Lifetime frequency of SAD in the overall sample was 12.7% (N = 24). Bipolar patients with comorbid SAD were younger than those without SAD (mean = 28.0 years, S.D. ± 5.9 vs. mean = 34.8, S.D. ± 10.7) (t = 2.28, df = 75, P < .03). Frequency of current (last month) comorbid SAD was 10.1% (n = 19). Level of awareness of illness among subjects with comorbid SAD at the time of the interview was fairly good (awareness of illness: 2.38 ± 1.28; awareness of therapy benefits: 2.04 ± 1.23; awareness of social consequences: 2.21 ± 1.28). These values may be compared to 4–5 on the 5-point scale, which are considered in the poor range. Table 1 shows that on four of the HSCL-90 subscales, patients with both bipolar disorder and SAD comorbidity had higher scores than those with bipolar disorder only: interpersonal sensitivity (P < .03), obsessiveness (P < .05), phobic anxiety (P < .03) and paranoid ideation (P < .02). A higher frequency of substance abuse was found among subjects with SAD comorbidity than among those without (37.5% vs. 18.8%, OR = 2.6, P < .03). Table 1. Demographic and clinical characteristics of patients (n = 189) with bipolar disorder (BD) without and with social anxiety disorder (SAD) comorbidity Bipolar disorder without comorbid SAD (n = 165) (N (%)) Bipolar disorder with comorbid SAD (N = 24) (N (%)) χ2 P-value OR (95% CI) Gender (female) 89 (53.9) 9 (37.5) 2.268 .132 0.5 (0.21–1.24) Married 47 (28.5) 2 (8.3) 4.430 .035 0.2 (0.52–1.0) Employed 59 (35.8) 7 (29.2) 0.400 .527 0.7 (0.29–1.89) Other Axis I comorbid disorders Substance abuse 31 (18.8) 9 (37.5) 4.397 .030 2.6 (1.04–6.47) Panic disorder 47 (28.5) 10 (41.7) 1.728 .189 1.8 (0.74–4.32) OCD 20 (12.1) 4 (16.7) 0.390 .532 1.5 (0.45–4.68) Mean ± S.D. Mean ± S.D. t P-value df Age (years) 36.6 ± 11.9 30.5 ± 7.3 3.446 .001 186 Age at onset of bipolar disorder 24.7 ± 8.0 21.4 ± 5.2 2.666 .011 186 Age at onset of first episode (depressive) 26.1 ± 9.0 20.4 ± 5.1 2.392 .019 80 Age at onset of first episode (manic) 23.5 ± 6.6 23.3 ± 5.3 0.114 .909 90 Number of depressive episodes 3.2 ± 2.6 3.3 ± 2.6 −0.087 .931 180 Number of manic episodes 3.1 ± 2.3 2.4 ± 1.7 1.322 .189 180 Duration of bipolar illness (years) 11.9 ± 9.7 8.96 ± 7.62 1.388 ns 186 HSCL-90 Somatization 1.0 ± 0.6 1.2 ± 0.8 −1.059 .292 127 Obsessiveness 1.2 ± 0.8 1.7 ± 1.0 −2.144 .043 127 Interpersonal sensitivity 1.0 ± 0.7 1.6 ± 1.0 −2.387 .027 127 Depression 1.2 ± 0.9 1.6 ± 0.6 −1.660 .099 127 Anxiety 1.2 ± 0.8 1.4 ± 1.0 −1.031 .335 127 Phobic anxiety 0.7 ± 0.7 1.1 ± 0.9 −2.254 .026 127 Anger-hostility 0.8 ± 0.7 0.9 ± 0.8 −0.489 .886 127 Paranoid ideation 1.1 ± 0.7 1.5 ± 0.97 −2.433 .016 127 Psychoticism 0.9 ± 0.7 1.2 ± 1.0 −1.832 .069 127 SCI-SAS-C total scorea 4.8 ± 3.2 7.7 ± 3.8 −2.250 .031 35 SCI-SAS-A total scoreb 4.6 ± 3.5 7.1 ± 3.68 −1.861 .071 35 Temporal relationship of onset of SAD with bipolar disorder Age of onset (years) of SAD (mean ± S.D.) Age of onset (years) of BD (mean ± S.D.) Preceded onset of BD (N (%)) Concurrent onset of BD (N (%)) Followed onset of BD (N (%)) Social anxiety disorder (n = 24) 11.9 ± 4.3 21.4 ± 5.2 23 (95.8) 1 (4.2) 0 a SCI-SAS-C = Structured Clinical Interview for Separation Anxiety Symptoms—Childhood section. b SCI-SAS-A = Structured Clinical Interview for Separation Anxiety Symptoms—Adulthood section. Table options In the bipolar group with comorbid SAD, mean age at onset of SAD was 11.9 ± 4.3; mean age of onset for bipolar illness was 21.4 ± 5.2. In 91.7% (N = 22) of subjects with both conditions, SAD onset occurred earlier than the onset of bipolar illness. SAD preceded the onset of panic disorder (PD) with or without agoraphobia in all of the 10 patients (41.7%) who had this additional diagnosis. In the four patients with SAD with a lifetime diagnosis of obsessive/compulsive disorder (OCD) (16.7%), SAD preceded the onset in all cases. As shown in Table 1, age at onset of first episode among bipolar patients who started with depression was earlier in the group with comorbid SAD than in the group without (20.4 ± 5.1 vs. 26.1 ± 9.0, P < .02). Age at onset of first episode among bipolar patients who started with mania did not differ significantly between the two groups (23.5 ± 6.6 vs. 23.3 ± 5.3, P < .91). Of the subsample of 46 bipolar subjects evaluated with the scale for childhood separation anxiety, the nine with comorbid SAD had higher scores on the SCI-SAS-C (childhood section) than those without SAD (respectively, 4.78 ± 3.20 vs. 7.66 ± 3.77, t = −2.250, df = 35, P < .03). A linear regression model was used with age at onset of bipolar disorder as the dependent variable and two blocks of different subset of independent variables. The first block contained SAD comorbidity, gender, duration of illness, number of manic episodes and number of depressive episodes. The second block contained the variables listed above plus PD and OCD comorbidity to control for effects of PD and OCD on age of bipolar disorder onset. The analysis showed a significant negative correlation of SAD with age at onset of bipolar disorder (β = −.189, t = −2.060, P < .04, 95% CI = −8.4/−0.16). Conversely, OCD was positively correlated with age at onset of bipolar disorder (β = .178, t = −4.004, P < .05, 95% CI = 0.5/9.4). No significant association of panic disorder and the other variables examined with age at onset of bipolar disorder was observed.