Personality correlates of impulsivity in subjects with generalized anxiety disorders

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Comprehensive Psychiatry 51 (2010) 538 – 545 www.elsevier.com/locate/comppsych

Personality correlates of impulsivity in subjects with generalized anxiety disorders Andrea Pierò⁎ Mental Health Department ASL TO 4, Mental Health Centre, Via Blatta 10, 10034 Chivasso, Italy

Abstract Background: As yet, the relation between personality traits and impulsiveness has not been investigated in subjects affected by generalized anxiety disorder (GAD). Method: A sample of 79 subjects with a diagnosis of GAD has been assessed at intake with Clinical Global Impression (CGI), Barratt Impulsiveness Scale (BIS-11), and with Temperament and Character Inventory. Comorbidity with cluster A or B personality disorders was excluded. Results: A multiple linear regression has identified 3 variables as independent predictors of impulsiveness: novelty seeking (NS) and reward dependence (RD) as for temperament and self-directedness (SD) as for character. Predictor analysis of the 3 subscales of BIS-11 showed that a higher NS is a predictor of all 3 subscales of BIS-11, whereas a higher RD is a protective factor for the attentive impulsiveness, and a low SD is predictive of a greater nonplanned impulsiveness. The CGI severity index is directly related to motor impulsiveness. Discussion: Preliminary results showed that in subjects with GAD only the motor component of impulsivity seems directly related to clinical severity, whereas impulsiveness is predicted by higher levels of 2 temperamental dimensions that are influenced by dopamine and norepinephrine systems and by weakness of character. Conclusion: Subjects with GAD showed an interesting variability in NS. Differences in levels of NS and of other temperament (RD) and character (SD) dimensions seem related to different degrees of behavioral inhibition and to a different impact of the cognitive components of impulsiveness. Clinical implications are discussed. © 2010 Elsevier Inc. All rights reserved.

1. Introduction Impulsivity is a complex and multidimensional feature that influences pathogenesis, course, and clinical severity of several mental disorders [1]. A pathologic increase of impulsivity is at the core of impulse control disorders, obsessive-compulsive disorders (OCDs), impulsive personality disorders (borderline personality disorder [BPD] and antisocial personality disorder), eating disorders [2], attention-deficit/hyperactivity disorder [3], and addiction disorders [4]. In bipolar disorders [5,6] and unipolar mood disorders [7], impulsivity was also identified as a significant psychopathologic dimension. In generalized anxiety disorders (GADs), though, the role played by ⁎ Dipartimento di Salute Mentale, ASL TO 4 Chivasso, Centro di Salute Mentale di Chivasso, Via Blatta 10, 10034, Chivasso, Italy. Tel.:+39 011 9176620; fax: +39 011 9176619. E-mail address: [email protected]. 0010-440X/$ – see front matter © 2010 Elsevier Inc. All rights reserved. doi:10.1016/j.comppsych.2010.02.003

impulsivity seems widely neglected, in spite of a growing body of data confirming the relation between anxiety and impulsivity [6,8]. Impulsivity is a dimension of extreme interest when it is studied as a personality trait [9]; in fact, impulsivity is rarely studied outside the spectrum of a disease-specific symptoms, but genetic [10] and neuroimaging studies [11] have identified impulsivity (especially in a diminished inhibitory control) as a possible endophenotype [12]. Recent evidences have highlighted the relevance of heritability: familial transmission of impulsivity has been demonstrated both within and outside the Diagnostic and Statistical Manual of Mental Disorders (DSM) categories of mental disorders [11]. Moreover, data from twin studies specifically support a genetic component of impulsivity [13]. A more recent twin study that assessed impulsivity using the BIS-11 self-report measure reported a heritability estimate of 0.44 [14]. Converging evidence, therefore, suggests that around 45% of the variance in self-reported impulsivity is accounted for

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by nonadditive genetic factors. The genetic contributions to impulsivity are mediated through numerous neurotransmitter systems; among these, the serotonin and dopamine systems seem to play a leading role [15-17]. A recent meta-analysis [18] showed that the functional variants of the dopamine D4 receptor gene may be associated with measures of impulsivity and novelty seeking (as assessed with Temperament and Character Inventory [TCI]). Psychological research has investigated impulsivity as a unitary psychological construct [11]. Some authors [19] have proposed an interesting conceptualization of impulsivity based on a 3-factor model, according to which impulsivity can be decomposed as a combination of attentional (“getting easily bored”), motor (“going into action”), and cognitive (“inability to plan”) factors. More recent theories [20] have decomposed impulsivity into 4 dimensions: (a) urgency, that is, the feeling of negative affects when resisting an urge; (b) lack of premeditation, that is, the inability to anticipate consequences; (c) lack of perseverance, that is, the inability to stick to one's task; and (d) sensation-seeking, that is, the experience of positive feelings toward risky actions. According to the 5-factor model of personality by Costa and McCrae [21], these 4 dimensions seem connected to different factors: urgency is related to higher neuroticism, whereas lack of premeditation and perseverance might be related to lower conscientiousness, and sensation-seeking might reflect higher extroversion [21]. In the 3-factor model by Cloninger et al [22], impulsivity as a temperament trait results from a combination of low harm avoidance (HA) and high novelty seeking (NS)—a high risk-seeking predisposition (NS) in subjects with a low level of temperamental inhibition (low HA) leads to an impulsive temperament (which is a highly heritable personality trait). Moreover, whenever subjects with low HA and high NS present a personality weakness (low selfdirectedness [SD]), the likelihood of impulsive personality disorders (cluster B of DSM-IV) increases [23]. Recent studies [24] on a sample of Italian subjects have showed that the character dimensions of SD and cooperativeness [C] were negatively related with impulsivity and anger, whereas NS was directly associated with impulsivity. Measures of impulsivity seem therefore strictly related to measures of temperament; a combined approach to this issue could to lead to the definition of an endophenotype of extreme clinical interest, identified through the assessment of impulsivity (motor and cognitive) and NS [25]. The endophenotype approach could contribute to the identification of diagnostic markers, help to create more homogenous diagnostic categories (or subtypes), and aid the identification of at-risk individuals for specific symptoms, behaviors, or treatment responses [11]. The aim of this study was to investigate the impulsivity dimension in subjects with GAD and the relation between temperament and character traits assessed with TCI and impulsivity. To the best of our knowledge, no data on the role of TCI-evaluated personality dimensions in relation to

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impulsivity in subjects with GAD are currently available in literature. According to the TCI, subjects with GAD are characterized by high HA and low SD [23] and share this quality with patients affected by panic disorder [26]. Our a priori hypothesis postulated the existence of a subgroup of subjects with GAD showing a high level of NS and a greater impulsivity risk. Because both personality dimensions and impulsivity could be related to the state psychopathology, such relation has been controlled not only for personality features but also for symptoms of anxiety and clinical severity at intake. 2. Materials and methods 2.1. Subjects Seventy-nine subjects with GAD were recruited among all outpatients with GAD referred to the Mental Health Center of Chivasso (Turin, Italy) between September 1, 2007, and June 1, 2009. Inclusion criteria were (1) a full diagnosis of GAD according to criteria of DSM-IV-TR [27], (2) age range between 18 and 55 years, (3) absence of acute full-syndrome Axis I disorders requiring inpatient treatment, (4) absence of actual addiction disorder [27], (5) absence of mental retardation, (6) absence of a cluster A or B personality disorder in Axis II [27], (7) absence of a bipolar disorder [27], and (8) willingness to give informed consent to participate in the study. Diagnostic assessment for Axis I and Axis II disorders had been carried out at intake by 2 trained psychiatrists, with the support of the Structured Clinical Interview for DSM-IV (SCID-OP I, and SCID II) [28-29]. Twenty-eight patients with GAD were excluded from the sample for the following reasons: (1) age out of the established range (n = 3); (2) comorbidity of an acute Axis I disorder (n = 12) requiring inpatient treatment, including mood disorders (n = 9), psychotic disorders (n = 2), eating disorder (n = 1); (3) comorbidity with mental retardation (n = 1); (4) presence of acute substance abuse disorder (n = 6); (5) presence of a bipolar disorder (n = 3); and (5) patients who met the inclusion criteria but refused to participate in the study or to sign an informed consent (n = 3). Subjects were assessed before the onset of outpatient treatment through the Clinical Global Impression (CGI) rating scale, and 2 self-administered questionnaires such as Barratt Impulsiveness Scale (BIS) and TCI. Two psychiatrists adequately trained in the use of the CGI and SCID-I and SCID-II rated all the subjects included in this study. All the procedures have been approved by a review committee. 2.2. Assessment instruments 2.2.1. Clinical Global Impression This is a well-known assessment tool [30], administered by clinicians to evaluate the severity of an illness (item 1),

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according to a score between 0 (nonassessed) and 7 (extreme severity). 2.2.2. Barratt Impulsiveness Scale The Barratt Impulsiveness Scale-Version 11 [19], which is currently one of the most used measures of impulsiveness, conceptualizes impulsiveness through the presence of 3 main components: a cognitive component, which is characterized by rapid shifts in attention and by impatience with complexity (attentive impulsiveness subscale, AI); a motor component, characterized by a tendency to act impetuously and without thinking or by inability to withhold responses (motor impulsiveness subscale, MI); and a nonplanning component, in which the individual does not plan or think carefully about the possible consequences of his/her actions (nonplanning impulsiveness subscale, NPI). 2.2.3. Temperament and Character Inventory The TCI [31,32] is an inventory divided into 7 independent dimensions. Four of these (NS, HA, reward dependence [RD], persistence [P]) assess temperament. Cloninger [22,23] refers to temperament as a set of emotional responses that are moderately heritable, stable throughout life, and mediated by neurotransmitter functioning in the central nervous system; such emotional responses provide a clinical description based on the scores attained by each subject with regard to a set of opposing temperamental features. Briefly, NS expresses the level of excitability, quick decisions based on incomplete information, extravagance, and quick-tempered dislike for rigid structures. High NS scores correspond to high explorative activity, lack of self control, impulsivity, and high responsiveness to novelty and high-sensation seeking, whereas low NS scores express the opposite characteristics. Harm avoidance reflects the efficiency of the behavioral inhibition system. Individuals with high HA are described as extremely careful, passive and insecure, and prone to react with a high rate of anxiety and depression to stressful events. Reward dependence reflects the maintenance of rewarded behavior. Individuals with high levels of RD are described as sentimental and easily influenced by others. P expresses maintenance of behavior as resistance to frustration. High P expresses the tendency to maintain unrewarded behaviors and correlates with rigidity and obsessiveness. The remaining 3 dimensions of the TCI (SD, C, and self-transcendence) are intended to evaluate character. Such character dimensions have been found to be as heritable as the 4 temperamental dimensions, with a heritability rate of about 50% in twin studies [23]. Briefly, SD expresses the degree to which the self is viewed as autonomous and integrated. C reflects the extent in which the self is viewed as a part of society. Self-transcendence expresses the degree to which the self is viewed as an integral part of the universe; generally, this dimension is displayed as an intuitive understanding of elevated aspects of humanity, such as compassion, ethics, art, and culture. Low SD and C scores appear to be the most important

Table 1 Sample description Variables

Mean

Range

Age Schooling CGI BIS TCI NS TCI HA TCI RD TCI PP TCI SD TCI CC TCI self-transcendence

37.4 ± 10.4 12.0 ± 2.2 4.2 ± 0.7 57.4 ± 8.6 21.5 ± 5.6 19.7 ± 6.6 15.7 ± 4.3 4.1 ± 1.2 27.8 ± 6.4 26.9 ± 4.6 13.9 ± 6.1

18-57 8-17 3-5 42-80 8-45 6-33 5-23 1-8 8-38 17-40 2-35

Males Females Not married Married Divorced Yes No Dysthymia Mood disorder NOS Panic disorder Eating disorder NOS Adjustment disorders No comorbidity

23 (29.1%) 56 (70.9%) 25 (51.0%) 21 (42.9%) 3 (6.1%) 23 (29.1%) 56 (70.9%) 8 (10.1%) 24 (30.4%) 10 (12.7%) 2 (2.6%) 10 (12.7%) 28 (35.4%)

Variables Sex Marital status

Axis II (cluster C) Axis I

n (%)

CGI indicates Clinical Global Impression at T0; GAF, Global Assessment of Functioning at T0; HAM-A, Hamilton anxiety total score; NOS, not otherwise specified.

predictors of categorical diagnosis of a DSM Axis II disorder [22,23]. All 7 dimensions of temperament and character have been found to have genetic determinants [23] and to be regulated by different brain systems according to the results of functional brain imaging [33]. Each dimension is influenced by complex interactions among genetic and environmental variables because individual personalities develop as complex adaptive systems [23]. The TCI test displays good psychometric properties also in the Italian version [32]. 2.3. Data analysis All data analyses were performed using the Statistical Package for Social Sciences (SPSS Inc, Chicago, Ill). The initial step was a description of our sample of GAD subjects (Table 1). An evaluation through a t test for independent samples has been made to compare males and females. Finally, a series of multiple linear regressions (stepwise forward) has been calculated to detect the independent predictors of overall BIS score (Table 2) and of the 3 subscales (AI, MI, and nonplanned impulsiveness [NPI]) of BIS (Tables 3-5). In multiple linear regression, clinical severity (CGI) at intake, schooling, and age were included among the independent variables as possible confounding factors.

A. Pierò / Comprehensive Psychiatry 51 (2010) 538–545 Table 2 Independent predictors of BIS total score at T0: multiple linear regression (stepwise forward)

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Table 4 Independent predictors of BIS subscale “MI” at T0: multiple linear regression (stepwise forward)

Model

R2

Variables

B

SE

T

Significance

Model

R2

Variables

B

SE

T

Significance

1

0.220

.000 .000 .000 .000 .000 .000 .000 .001 .010

2

0.175

15.145 0.285 7.427 0.318 1.673

2.030 0.091 3.788 0.089 0.702

7.458 3.141 1.961 3.570 2.384

.000 .002 .048 .001 .020

0.481

10.14 4.56 11.66 6.65 −4.45 9.995 6.245 −3.320 −2.656

Constant NS Constant NS CGI

3

3.875 0.175 3.470 0.136 0.170 5.092 0.177 0.141 0.141

0.114

0.386

39.13 0.797 40.46 1.20 −0.606 50.67 1.105 −0.467 −0.375

1

2

Constant NS Constant NS RD Constant NS RD SD

For 1, predictors: (constant) and NS; 2, predictors: (constant), NS, and RD; and 3, predictors: (constant), NS, RD, and SD. Variables included in the analysis were TCI, age, schooling, and CGI at T0.

3. Results 3.1. Sample description Table 1 represents the full sample of patients included in this study. Only 29.1% of subjects present an Axis II disorder of cluster C (Table 1), whereas the 64.6% present an Axis I comorbidity (Table 1). Mean and standard deviation of CGI, TCI subscales, and BIS total score at T0 are also indicated in the table. A comparison through t test for independent samples between males and females was made; no significant difference emerged between the 2 groups of sexes both in categorical variables (Axis I comorbidity; Axis II comorbidity) and in continuous variables (TCI 7 dimensions, CGI, age, schooling, BIS total score, BIS 3 subscales). Therefore, sex was not considered a confounding variable in regression analysis (data will be available for interested readers upon request). 3.2. Predictors of impulsiveness (BIS) A linear multiple regression (stepwise forward) showed (Table 2) that only 3 variables (at intake) predicted the level of impulsiveness (BIS) in the full sample: (1) NS, (2) RD, and (3) SD. The first variable showed a direct correlation with BIS total score, whereas the other 2 showed an inverse correlation.

Table 3 Independent predictors of BIS subscale “AI” at T0: multiple linear regression (stepwise forward)

For 1, predictors: (constant) and NS; 2, predictors: (constant), NS, and CGI. Variables included in the analysis were TCI, age, schooling, and CGI at T0.

3.3. Predictors of the 3 subscales of BIS The relation among variables at intake and the score in the 3 subscales of BIS (AI, MI, NPI) has been explored with multiple linear regression methods. As concerns the “attentive impulsiveness” subscale (AI), 2 predictors have been identified: NS and RD. Also, for the “motor impulsiveness” (MI) subscale, 2 predictors were identified: NS and CGI. Predictors for “nonplanned impulsiveness” (NPI) were SD and NS. These data are illustrated in Tables 3, 4, and 5.

4. Discussion Impulsiveness can be defined as the predisposition to respond to internal or external stimuli without regard to the potentially negative consequences for the individual or other subjects [9]. There is growing evidence that impulsiveness is not a unitary trait but a mixture of 2 core components or dimensions: (1) a difficulty to inhibit action and motor responses (impulsive actions) or behavioral inhibition and (2) a propensity to impulsive decision making associated with intolerance toward delay or delay aversion, exemplified by an increased preference for immediate reward over more beneficial but delayed reward [10]. Nevertheless, as others have stated, impulsiveness could also be the result of an interaction among multiple and heterogeneous components: this leads to a lack of consensus in its operational definitions and to divergences in assessment [34]. In the last decade, there has been increasing attention toward impulsiveness traits in mental disorders [10]. Particularly, researchers have demonstrated that (1) impulTable 5 Independent predictors of BIS subscale “NPI” at T0: multiple linear regression (stepwise forward)

Model

R2

Variables

B

SE

T

Significance

Model

R2

Variables

B

SE

T

Significance

1

0.185

1.565 0.070 1.480 0.077 0.058

6.413 4.099 7.01 5.34 −3.16

.000 .000 .000 .000 .002

0.159

0.283

10.03 0.289 10.37 0.411 −0.184

1

2

Constant NS Constant NS RD

2

0.263

Constant SD Constant SD NS

27.68 −.313 21.18 −0.301 0.292

2.381 0.084 3.023 0.079 0.091

11.62 −3.742 7.08 −3.818 3.207

.000 .000 .000 .000 .002

For 1, predictors: (constant) and NS; 2, predictors: (constant), NS, and RD. Variables included in the analysis were TCI, age, schooling, and CGI at T0.

For 1, predictors: (constant) and SD; 2, predictors: (constant), SD, and NS. Variables included in the analysis were TCI, age, schooling, and CGI at T0.

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siveness is a transnosographic dimension that presents several features of the endophenotypes [11]; (2) impulsiveness is of extreme relevance for assessing the severity of mental disorders, especially in the case of suicidality [34-38] and antisocial behaviors [39]; (3) stronger impulsiveness may decrease response and adherence to treatments [40] even without a comorbidity with a personality disorder in Axis II of DSM-IV [27]; and (4) a specific treatment of impulsiveness might represent a novel intervention strategy for several mental disorders [10]. Because GAD is a highly prevalent condition in many populations, producing heavy individual and societal costs, as well as a marked level of impairment—equivalent in magnitude to that observed in patients with major depressive disorder [41]—the scarcity of data about impulsiveness traits in this disorder is somewhat surprising. In anxiety disorders other than OCD, nevertheless, this dimension has been widely neglected. Some evidences suggest a relation between anxiety and impulsiveness; in bipolar disorders, a broad range of anxiety-related symptom domains was shown as associated with greater impulsiveness [6], and patients with a comorbidity anxiety disorder displayed significantly higher levels of impulsiveness relative to patients without an anxiety disorder [6]. Anxiety and impulsiveness are the 2 main risk factors in suicidality [8,42]; suicide risk in individuals with anxiety disorders is high [43,44], though often not assessed by the therapist [45]. Other researchers have stated that a number of adolescents with at-risk behavior might be categorized as belonging to an impulsive-anxious group [46] showing a higher inclination to suicidality or other severe self-aggressive behaviors. According to the authors of this study, such a subgroup is closely related to the soft bipolar spectrum. Four main evidences emerged from the data analysis: (1) as expected, a high level of NS is the stronger personality predictor of impulsiveness in subjects with GAD, and NS results implicated in all 3 components of impulsiveness in the BIS-11 questionnaire (AI, MI, NPI); (2) a higher RD seems to work as a protective factor, particularly for the attentive components of impulsiveness; (3) lower SD increases the risk of impulsiveness, and seems to play a marked role in NPI; and (4) clinical severity seems to be relevant only in MI. Novelty seeking expresses the level of activation of exploratory activity. Subjects with high NS scores present a high explorative activity, a tendency to take quick decisions based on incomplete information, and a certain extravagance. Moreover, high NS scores indicate a strong inclination to take risks, lack of behavioral inhibition, dislike for rigid structures, and impulsive behavior (irrespective of possible negative consequences). High levels of NS have been reported in subjects affected by impulse disorders, particularly substance addiction [47], BPD [48,49], and eating disorders of the purging/binging type [50,51]. Novelty seeking is mediated by dopamine neurotransmitter function-

ing in the central nervous system [23]. The behavioral inhibition (MI) component of impulsiveness is strictly regulated by the dopaminergic modulatory control [11], and it could be possible that shared dopaminergic pathways regulate NS and impulsiveness levels. Subjects with GAD, high NS levels, and a greater tendency to impulsive behaviors and reactions might therefore present a genetic liability to dopamine pathways alteration [18]. Because in previous studies NS was related with impulsiveness [24], these data seem to give further evidence to the association; particularly, the presence of variable NS levels among GAD subjects and the close relationship between this variability and the impulsiveness components of the BIS-11 subscales seems noteworthy. Reward dependence reflects the degree of adherence to rewarded behavior. Individuals with high levels of RD are described as sentimental, dependent, and easily influenced by others [23]. In our study, a higher score in this dimension seems to be an independent predictor of lower AI. When the well-known temperamental predisposition to insecure attachment in subjects with GAD is combined with a stronger temperamental predisposition to difficulties in building close relationships, these subjects might denote a higher risk of impulsiveness, especially in its attentive component. These data seem to confirm previous evidences [24,52] sustaining the role of secure attachment and RD, with a good resilience as a protective factor [53]. Along with other researchers, the authors of the TCI suggest that RD is correlated with low noradrenergic activity [31]; presently, the relation between impulsiveness and noradrenergic pathways is still controversial, mainly because of the uncertain role played by the genetic variants of the 5hydroxytryptamine transporter (5-HTT)–linked polymorphic region on this dimension [54]. Nevertheless, the results of our study indicate that this neurotransmitter pathway could play a specific role in the cognitive component of impulsiveness, regardless of serotonin activity. Harm avoidance reflects the efficiency of the behavioral inhibition system, and it is related to serotonergic activity [22,23], but no significant relations between HA and impulsiveness emerged from this study. It must be remembered that in GAD the level of HA is usually relevant [23]. Because all subjects with GAD have high levels of HA (with a significant lack of low scores), this dimension cannot be considered a predictor of higher or lower impulsiveness; however, its role is undoubtedly relevant and should be clarified by further enquiries. On the whole, the results of this study seem to indicate that the 3 major neurotransmitters (serotonin, dopamine, and norepinephrine) play a multiple and integrated role in the predisposition to impulsiveness in subjects with GAD and that the heterogeneity of these neurotransmitter pathways (due to genetic and environmental influences) could account for the differences in temperamental dimensions (NS and RD) [55] and for their correlations with the subcomponents of impulsiveness.

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Self-directedness, a core dimension of TCI, has been demonstrated to be a specific independent predictor in nonplanning impulsiveness (Table 4). Nonplanning impulsiveness arises from difficulties in thinking and planning the consequences of individual actions and is related to an overall weakness of self-control and behavioral inhibition. This seems to confirm the efficacy of the SD dimension in detecting all aspects of character related to immaturity and defective personality development (strength of ego, impulse control, self-esteem, and self-efficacy). In fact, a low level of SD is a typical trait of subjects with personality disorders, particularly BPD [23,49], and subjects with low SD are described as immature, insecure, and unstable; on the emotional level, they are often irresolute, unable to modify their behavior, impulsive [22,56], and at risk of suicide [57]. Subjects with low SD and low C have a high risk of developing a personality disorder [23]. The results of this study confirm that the character dimension of SD is negatively related with impulsiveness [24] also in subjects without a cluster B personality disorder (eg, BPD). The knowledge acquired on high NS and low SD as possible predictors of impulsiveness seems to implicate a comorbidity with BPD in our sample. The subgroup of patients with GAD and higher impulsiveness levels might present a borderline personality organization [58]. The temperamental core of impulsiveness described in the study (high NS, low RD, and low SD), which accounted for almost 50% of the variance in impulsiveness, could be related, in a way still unknown, to this construct [59]. Further studies are obviously needed to confirm this hypothesis. Some studies have showed that the character dimensions are strongly related with recently evolved regions of the brain, such as the frontal, temporal, and parietal neocortex, which regulate learning of facts and propositions [33]; this could account for the relationship between low SD and nonplanning impulsiveness, although further evidences are clearly needed. Cloninger [23] has found that people who score high on all 3 character traits show higher levels of wellbeing (as measured by presence of positive emotions, absence of negative emotions, satisfaction with life, or virtuous conduct) when compared to other subjects. Finally, in several diseases (not only in mental disorders), low SD levels have been identified as indexes of severity [60,61] or dropout to treatment [62] or have proved useful in disorder subtyping [50,63]. As regard the role of clinical severity in MI, a higher level of anxiety symptoms in subjects with GAD might result in a higher risk of impulsive reactions and behaviors. In a subgroup of subjects with GAD, higher levels of anxiety symptoms (as measured with CGI) and clinical severity do not affect the cognitive component of impulsiveness (difficulties in attention and in planning the consequences of one's actions) but lead to a higher level of MI (impulsive actions, motor disinhibition). This bears some resemblance with the typical traits of OCD (compul-

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sive behaviors), but further studies are needed to confirm this preliminary evidence. 4.1. Limits This study has some limitations. First of all, the small size of the sample studied prevented us from analyzing the role of comorbidity. The exclusion of severe depressive disorders, as well as of bipolar or psychotic subjects, was decided to restrain the influence of such conditions on HA and NS levels [64]. The lack of a more specific assessment of anxious and depressive symptoms other than CGI can be mentioned as a further limit. Finally, the lack of a control group could be identified as a substantial shortcoming, which might perhaps be excused in a pilot study opening the way to deeper investigations. 4.2. Conclusion Identification of impulsiveness predictors might allow us to differentiate among subgroups of patients with GAD who, despite sharing the same diagnosis, need different and specific approaches to the treatment of such dimension. An adequate, tailored pharmacologic and psychologic treatment of impulsiveness traits in subjects with GAD could produce a better response to therapeutic efforts, as well as reduce the risk of dropout, self-harm, or suicidality. In particular, subjects with low SD could benefit from a specific psychotherapeutic approach aimed at improving self-control and self-efficacy [23], therefore, reducing nonplanning impulsivity; as for medication, these data seem to prove the usefulness of treatment strategies influencing also dopamine and norepinephrine pathways. In particular, drugs acting on norepinephrine pathways (eg, reboxetine and duloxetine) that were showed by previous studies as effective on impulsivity [65,66] could also be used in subjects with GAD and higher levels of AI. Further studies are obviously needed to clarify the role of impulsiveness in GAD and to help clinicians in the choice of the best pharmacologic or psychologic treatment. References [1] Cale EM. A quantitative review of the relations between the ‘‘Big 3’’ higher order personality dimensions and antisocial behavior. J Res Pers 2006;40(3):250-84. [2] Boisseau CL, Thompson-Brenner H, Eddy KT, Satir DA. Impulsivity and personality variables in adolescents with eating disorders. J Nerv Ment Dis 2009;197(4):251-9. [3] Zepf FD, Stadler C, Demisch L, Schmitt M, Landgraf M, Poustka F. Serotonergic functioning and trait-impulsivity in attention-deficit/ hyperactivity-disordered boys (ADHD): influence of rapid tryptophan depletion. Hum Psychopharmacol 2008;23(1):43-51. [4] de Wit H. Impulsivity as a determinant and consequence of drug use: a review of underlying processes. Addict Biol 2009;14(1):22-31. [5] Najt P, Perez J, Sanches M, Peluso MA, Glahn D, Soares JC. Impulsivity and bipolar disorder. Eur Neuropsychopharmacol 2007;17 (5):313-20.

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