Panic-agoraphobic Spectrum Symptoms are Associated with Impulsivity in Bipolar Disorder

  

    
PAS    dimension
    
BD I
    
BD II
    
MDD
  
  

    
Separation    sensitivity
    
.336**
    
.296**
    
.264*
  
  

    
Typical    and atypical panic-like symptoms
    
.458**
    
.279*
    
.251*
  
  

    
Stress    sensitivity
    
.375**
    
.188
    
.274*
  
  

    
Substance    and medication sensitivity
    
.364**
    
.343**
    
.287*
  
  

    
Anxious    expectation
    
.270*
    
.285*
    
.302**
  
  

    
Typical    and atypical agoraphobia
    
.227*
    
.194
    
.307**
  
  

    
Illness    phobia and hypochondriasis
    
.204
    
.182
    
.266*
  
  

    
Reassurance    orientation
    
.531**
    
.340**
    
.258*
  
  

    
PAS    Total
    
.465**
    
.359**
    
.345**
  
  

    
** p<�    0.01�� * p< 0.05
    
 
  

Table 4:  Impulsivity dimension and PAS-SR domains.

Discussion and Conclusion

Impulsivity is an individual’s primal behaviour [45,46] and seems to be an essential part of control disruptive disorders [47] substance abuse [15] personality disorders [48] aggressive behaviours [49,50] bipolar disorder [51] suicidal behaviour [52] and some other potential violent and explosive behaviours [53]. Impulsivity is the rule and not the exception, like in our research, in BD and represents a core feature of BD [1,5,7,54] being a prominent component of mania and mixed mania [9,10] Still, impulsivity seems also to contribute to BD complications, such as suicide [11-13] and substance abuse [1,15-17]. Impulsivity displays a positive relationship with anxiety [24,25,55], impulsivity could be a stable trait in euthymic BD and a better trait impulse control may be associated with better treatment responsiveness [55-58]. It has been traditionally stated that impulsivity displays a negative relationship with anxiety [18,19] and epidemiological data revealed high rates of comorbidity between anxiety disorders and impulse control disorders [21,22]. Of note, BD patients with a comorbid anxiety disorder seem to display significant higher levels of impulsivity when compared to patients without an anxiety disorder [22]. Moreover, the level of depression is significant in the intensity of impulsivity and anxiety, and the presence of anxiety, either as a comorbid disorder or as current anxiety symptoms, is associated with higher impulsivity in subjects with either BD or MDD [23,54]. In particular, epidemiological data demonstrated that panic disorder occurs frequently in BD and in some studies such a comorbidity seems to represent the rule rather than the exception [27,28]. Panic disorder comorbidity is BD is associated with poor response to treatment, earlier onset of BD, elevated rates of comorbid psychopathology, greater levels of depression, more suicidal ideation and increased familial risk of affective disorder [29,30]. Our data suggest not only that bipolar panic comorbidity but also that subthreshold panic symptoms in BD patients, constitutes a unique entity from a clinical, neurobiological and genetic point of view [31,32]. Moreover, euthymic BD patients with particular addictive and anxiety comorbid disorders have large number of depressive episodes, rapid cycling, mood instability, and high risk of suicidal behaviour [14].

Anxiety comorbidity and impulsivity

To our knowledge the majority of the literature study pay attention on mood disorder sample (bipolar disorder and major depressive disorder), especially to suicide-aggressive behaviours [59-62], nevertheless without a significant correlation to anxiety comorbidity.

Into the literature, the correlation of anxiety comorbidity and impulsivity in a sample of bipolar disorder is investigate by the single article of Taylor et al [22], in which the confirmatory regression analyses controlling for age, gender, current substance use disorder status, and presence or absence of a current mood episode entered together, all anxiety-related measures continued to provide unique significant prediction of the BIS total score (b range = .23–3.18, t range = 2.18–4.03, all p < .05). None of the added covariates, however, were significantly associated with the BIS total score.

It has been traditionally stated that impulsivity displays a negative relationship with anxiety [18,19]. This was mainly based on the assumption that anxiety alerts the individual to potential danger, and operates to inhibit behavior under conditions of heightened threat [20]. In reality, epidemiological data revealed high rates of comorbidity between anxiety disorders and impulse control disorders [21,22]. Moreover patients with impulse control disorders explain more anxiety arousal and tension before to commit impulsive acts [5], and this suggest a direct link between anxiety and impulsivity in bipolar disorder. Of note, BD patients with a comorbid anxiety disorder seem to display significant higher levels of impulsivity when compared to patients without an anxiety disorder [22].

Impulsivity and polarity of affective state

Euthymic bipolar patients express trait impulsivity at higher levels than healthy individuals [51], but they do not differ from manic bipolar patients [63]. Manic and eutimic bipolar patients present higher impulsivity level than healthy controls at BIS-11 factors: ‘attention’, ‘motor’ e ‘non planning impulsiveness’ [16,51,63,64]. Although anxiety disorder comorbidity may be critical for identifying high-risk bipolar patients, many important, well-designed studies of Suicidal Ideation and Suicidal Attempts in bipolar disorder have not examined the relationship of anxiety comorbidity with SA and SI [59- 62].

By the use of MOOD-SR lifetime, and the rational creation of this impulsivity dimension, we can confirm that impulsivity is a stable component in mood disorders beyond illness episodes (manic, depressive and mixed state). In bipolar patients impulsivity seems to be much higher than depressive patients [51,63,64] and important during the illness episodes but also during the eutimic phase of the illness [1,51,63]. Aggressive behaviors and impulsive acts are relate at bipolar manic state [65]. These data suggest that, in bipolar disorder, impulsivity has both state- and trait- dependent components, and is present irrespective of illness phase [51,63]. These remarks highlight tree important reports: a) impulsivity is independently of illness phase; b) the association between impulsivity and bipolar disorder is a stable component during eutimic state, and this suggest that impulsivity is independent psychopatological dimension from illness course and mood disorder clinical symptoms; c) impulsivity could underlie a specific clinical characteristics and illness bipolar course with a specific neurobiological mechanism [51,66,67]. Bipolar- impulsivity connection should be due to continuous mood fluctuations, in particular to manic phase [1,16,63,68] with a key role during suicidality in greater depressive episodes [39]. Second this could be an independent features correlated to noradrenergic function in bipolar disorder [69,70] that is higher during manic episodes [66,71], and settle specific mood disorder endophenotipes [51,67].

Both possibility are important to a better comprehension of bipolar disorder [51,63]. These possibility should be important to a better understand for bipolar disorder [51,63] and impulsivity could shape course and presentation of bipolar disorder. Moreover trait impulsivity seems contribute to less therapeutic compliance and worse outcome [64].

Impulsivity and panic-agoraphobic spectrum

The panic-agoraphobic spectrum focused on its importance in identifying phenotypes of depressed patients who might present differently and respond differently to treatment. In such a situation, the authors consider identification of spectrum symptoms especially important because they may occur in the absence of diagnosable PD and still define an important depressive phenotype [30]. In the clinical practice, the spectrum model is extremely useful, even at the light of previous studies [72,73] thought some features, like affective instability and anxiety disorder comorbidity in bipolar patients, show complex clinical case with major severity and worst course [74,75].

Moreover clinically significant lifetime panic spectrum was associated with female sex, higher levels of depression, a greater risk of suicidality, and a much longer time to remission of the index mood episode [30]. The spectrum approach, however, was developed to provide a more dimensional assessment of underlying symptom constellations. Categorical classification of panic disorder often fails to capture the broad array of atypical symptoms and related, yet enduring, temperamental features that can be associated with this core condition. In contrast, the PAS-SR casts a “wide net” to capture the lifetime experience of both classic panic symptoms as well as related, yet subtle, manifestations of this core condition [30]. This may be advantageous, given the contention of Akiskal, Savino and others, that the affective instability and common anxiety-mood comorbidities of patients with BP disorder are often misdiagnosed as Axis II personality disorders, such as borderline personality disorder [30].

Moreover the assessment of a broad range of panic features (in particular atypical symptoms) than those represented by the DSMIV criteria for panic disorder, seems to be an indicator of impulsive behaviours in bipolar disorder.

These represent a crucial point not only in mixed and depressed patients also too in bipolar eutimic patients where trait impulsivity is higher than healthy individuals [51].

Our clinical experience suggests that patients who are more sensitive to medical reassurance are generally those at the onset of the disorder, who present with a limited number of symptoms and are mostly concerned about an underlying physical illness not yet identified. These patients tend to ask repeatedly for lab tests or visits [76].

In our sample, bipolar I and II eutimic patients explain impulsivity correlated with reassurance orientation, substance and medication sensitivity and panic-like symptoms. Indeed impulsivity dimension we look into BIS-11 order factor motor impulsiveness and non-planning impulsiveness, and this would be interesting because identify a specific endophenotipe among bipolar disorder patients “that tested themselves in dangerous situations”, “that are more impulsive to reduce anxiety symptoms”.

Limits of our study is: 1) only a 19,8% (49 patients of the total, 11 bipolar I, 15 bipolar II and 23 unipolar) of the sample show a panic disorder comorbidity following DSM-IV criteria, and in our knowledge is lower than literature data [more than half (51.2%) of patients with BD were identified as having a co-occurring anxiety disorder at some point in their lifetime, while 30.5% were diagnosed as having a current anxiety disorder [26]; 2) The impulsivity dimension used here was rationally constructed by reviewing MOOD-SR items based on items of Barratt Impulsiveness Scale (BIS-11) (Table 3). Between this dimension we essentially check on motor-impulsiveness and non�planning impulsiveness order factors in the BIS-11 [43]; 3) We don’t examine axis II comorbidity, because our intent was to study trait impulsivity in eutimic bipolar patients.; 4) we corroborate the conclusions of Taylor et al., [22], and we overcome a limit of this previous study, to be more precise the low size of bipolar patients, the lack of unipolar patients inside the sample; 5) we don’t examine substance and alcool abuse disorders, and suicidality wherefore the lower percent of substance/alcool abuse disorders, and aggressive behaviours; 6) we don’t examine the axis II disorder comorbidity; 7) next our propose would to value the correlations between BIS-11 and impulsivity dimension in a subsample of bipolar patients, to confirm internal validity of impulsivity dimension.

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