Impulsivity in Bipolar and Substance Use Disorders Mustafa Ozten, Atila Erol, Semra Karayılan, Hilal Kapudan, Ertac Sertac Orsel, Neslihan Akkisi Kumsar PII: DOI: Reference:
S0010-440X(15)00020-6 doi: 10.1016/j.comppsych.2015.02.013 YCOMP 51485
To appear in:
Comprehensive Psychiatry
Received date: Revised date: Accepted date:
3 September 2014 11 February 2015 16 February 2015
Please cite this article as: Ozten Mustafa, Erol Atila, Karayılan Semra, Kapudan Hilal, Orsel Ertac Sertac, Kumsar Neslihan Akkisi, Impulsivity in Bipolar and Substance Use Disorders, Comprehensive Psychiatry (2015), doi: 10.1016/j.comppsych.2015.02.013
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Impulsivity in Bipolar and Substance Use Disorders
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Sakarya University, Faculty of Medicine, Department of Psychiatry, Sakarya, Turkey
Sakarya University Training and Research Hospital Psychiatry Clinic, Sakarya, Turkey
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Mustafa OZTEN, (Corresponding Author)
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b
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Akkisi Kumsarb
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Mustafa Oztena , Atila Erola, Semra Karayılana, Hilal Kapudana, Ertac Sertac Orsela, Neslihan
M.D. Sakarya University, Faculty of Medicine, Department of Psychiatry, Sakarya, Turkey Phone:
+905443727947
E-Mail: [email protected] Atila EROL,
Sakarya, Turkey
Semra KARAYILAN,
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E-Mail: [email protected]
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Professor of Psychiatry, Sakarya University, Faculty of Medicine, Department of Psychiatry,
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M.D. Sakarya University, Faculty of Medicine, Department of Psychiatry, Sakarya, Turkey E-Mail: [email protected] Hilal KAPUDAN,
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M.D. Sakarya University, Faculty of Medicine, Department of Psychiatry, Sakarya, Turkey E-Mail: [email protected] Ertac Sertac ORSEL,
M.D. Sakarya University, Faculty of Medicine, Department of Psychiatry, Sakarya, Turkey E-Mail: [email protected] Neslihan Akkisi KUMSAR, M.D. Sakarya University Training and Research Hospital Psychiatry Clinic, Sakarya, Turkey E-Mail: [email protected]
ACCEPTED MANUSCRIPT Impulsivity in Bipolar and Substance Use Disorders
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Abstract
Background: Bipolar disorder (BD) is commonly associated with increased impulsivity, particularly during manic and depressed episodes also impulsivity remains elevated during
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euthymic phases. Impulsivity is also a factor in the initiation and maintenance of substance use disorders (SUD). Impulsivity can predispose to substance abuse or can result from it. Impulsivity
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appears to be relatively independent of mood state and is higher in individuals with past substance use. So we wanted to compare in terms of impulsivity of BD and SUD closely associated with impulsivity and determine if any differences.
Methods: Impulsivity was evaluated by the Barratt Impulsiveness Scale (BIS-11A), in 35
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bipolar interepisode disorder male patients without any comorbid substance use disorder, 40 substance use disorder male patients. The BIS-11A mean scores for two groups were compared
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through one-way between-groups ANOVA.
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Results: There were no difference among the BD and substance use disorder on total and subscale attentional, motor impulsivity measures. However, for male patients there were difference on the nonplanning subscale. Male BD patient group scored higher than the male substance use
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disorder patient group for nonplanning impulsivity.
Conclusions: Our results replicate that interepisode BD and substance use disorder patients both have increased total impulsivity and extends them that trait impulsivity is not completely the same in subscales. Both groups were similar on attention and motor impulsivity subscales but on the nonplanning subscale BD patients are more impulsive than the substance use disorder patiens.
Keywords: Impulsivity; Bipolar disorder; Substance use disorder.
ACCEPTED MANUSCRIPT 1.Introduction Impulsivity is a disposition toward rapid, unplanned reactions to internal or external stimuli without regard to the negative consequences of these reactions to the self or to others [1] . Even though impulsivity is not itself a psychiatric diagnosis, it seems to be more common in some mental
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disorders such as certain personality disorders, bipolar disorders, impulse-control disorders (ICD)
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and substance abuse.
Impulsivity is a frequent component of the course and presentation of bipolar disorder; it has therefore been proposed to represent a core feature of the illness that persists across different
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affective states [1–8]. Among bipolar patients, impulsivity appears to be especially important during manic episodes, but may also be found during euthymia and other mood phases [1,2,9]. Both the
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impulsivity that appears in the manic phase of bipolar disorder (state impulsivity) and the stable impulsivity that may extend across mood states (trait impulsivity) are important features of bipolar disorder. Euthymic bipolar patients express trait impulsivity at higher levels than healthy individuals [9], but they do not differ from manic bipolar patients [3]. These findings indicate that the impulsivity found among bipolar patients may be independent of mood state.
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There is now widespread agreement that impulsivity plays a key role in the initiation and development of substance misuse problems. Impulsivity can predispose to substance abuse, and can
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result from it [10]. Substance users are known to be highly impulsive and this is reflected in their BIS-11 scores. Behavioral and rating scale measures of impulsivity are elevated in patients with
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substance abuse [11,12]. For instance increased impulsivity are found for cocaine dependent adults [13] and ecstasy users [14] relative to controls.
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Impulsivity, which is prominent in both bipolar disorder and substance abuse, may have behavioral and biological substrata that contribute to the overlap between the two disorders [1]. So in this study our goal was to compare impulsivity scores of patients with BD and SUD. Our hypothesis is BD and SUD have different impulsivity rates and profiles.
2. Methods
2.1 Participants 35 euthymic (interepisode) BD patients without any SUD and 40 euthymic SUD patients were recruited from the outpatient psychiatry clinic of Sakarya University Faculty of Medicine. BD and SUD diagnoses were obtained using the Structured Clinical Interview for DSM-IV diagnoses. Inclusion criteria were: (i) 18 years of age or older; (ii) diagnosis of euthymic BD without SUD comorbidity and SUD
ACCEPTED MANUSCRIPT without bipolar comorbidity; Exclusion criteria for all groups were: (i) presence of chronic illness (e.g., hypertension, diabetes, liver disease, kidney diseases, current thyroid dysfunction, or neurological disease); (ii) current comorbid Axis I disorders. All procedures were carried out after participants had demonstrated adequate understanding and provided written informed consent.
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For BD patients; diagnoses and mood state were verified with the Structural Clinical Interview
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for DSM-IV [15], the Hamilton Rating Scale for Depression, 21 items (HAM-D) [16], and the Young Mania Rating Scale (YMRS) [17]. Absence of mood symptoms at least one month before the interview, as well as scores of < 6 on the HAM-D and the YMRS scales, defined euthymia.
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SUD group were recruited from among patients applied by probation. Diagnosis of substance use disorder was made according to the Structured Clinical Interview for DSM-IV diagnoses. There
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was no substance use history, withdrawal symptom of substance and substance craving at least 3 months before the clinical interview. Patients were required to provide urine samples free of substances six times at intervals of 1 week. Urine samples were analyzed for cannabinoids and synthetic cannabinoids, cocaine, amphetamine, ecstasy, barbiturates, benzodiazepines, ethyl glucuronide, phencyclidine and opiates at our University Departmental Chemical Analysis
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Laboratory using the Enzyme Multiple Immunoassay Technique- Drug Abuse Urine assay. So they were not under the effect of any substance at their assessments. None of the SUD group were taking
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psychotropic medications for prophylaxis or anticraving at the time of assessment.
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2.2 Methods
Participants completed the Barratt Impulsiveness Scale version 11A (BIS- 11A) [18] to assess
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impulsivity. The BIS-11A is a 21-item self-report inventory that measures impulsivity as a trait encompassing three domains: attentional impulsivity (intolerance for complexity and persistence); motor impulsivity (tendency to act without forethought); and non-planning impulsivity (lack of a sense of the future). Items are rated from 1 (absent) to 4 (most extreme).
2.3 Statistical analysis All analyses were performed using the Statistical Package for the Social Sciences, version 16 for Windows (SPSS, Inc., Chicago, IL, USA). The two groups were compared using one-way betweengroups ANOVA. The level of significance was set at p = 0.05.
3. Results
3.1 Demographic Data 35 BD patients mean age 36,43 ± 14,08 and 40 SUD patients mean age 29,65 ± 10,2, age of
ACCEPTED MANUSCRIPT onset BD was 29,94 ± 13,07 and age of SUD was 21,15 ± 5,4, all patients was male. 31 BD and 29 SUD patients live in urban and 4 BD, 11 SUD patients live in rural area. The mean HAM-D score was 2.86±0.95, and the mean YMRS score was 1.91±0.76. Demographic and clinical characteristics of the 2 groups are displayed in table 1. Mean age of BP group was higher than the
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mean age of SUD group (t=2.40; DF=73; p=0.02).
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Table 1.
SUD group data show that 28 (%70) patients used cannabinoid and synthetic cannabinoid, 3 (%7,5) patients used ecstasy, 2 (%5) patients used heroine, 1 (%2,5) patient used cocaine. 6 (%15) patients used multiple substances. BD group were all receiving maintenance treatment. 27 (%77) of them were receiving lithium and mean dose was 900 mg/day. 12 (%34) lithium-treated patients also were receiving additional atypical antipsychotic treatment. Risperidone 3mg/day (mean dose), quetiapine 400 mg/day (mean dose) and olanzapine 10 mg/day (mean dose) was preferred. 8 (%23) of BD patients were receiving valproate and mean dose was 750 mg/day. 4 (%11) of valproate-treated patients also were receiving additional atypical antipsychotic medication. Risperidone 2 mg/day (mean dose) and quetiapine 300 mg/day (mean dose) were preferred.
ACCEPTED MANUSCRIPT 3.2 Group comparisons The BD and SUD groups scored similarly on total impulsivity measures (p>0.3) (Table 2 ). The BD and SUD groups did not differ regarding motor impulsivity (p>0.7) and attentional impulsivity (p>0.2). On the non-planning subscale there were difference among the BD and SUD; groups
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scored differently (p =0.04). Male BD patient group scored higher than the male substance use
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disorder patient group for nonplanning impulsivity; and this difference remains significant when the influence of age was controlled with ANCOVA.
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Table 2.
ACCEPTED MANUSCRIPT 4. Discussion Impulsivity is related to mechanisms and consequences of affective symptoms [1,19]. Impulsivity is
considered to be inherent in mania and is a prominent part of its diagnostic criteria [9,
15]. There is evidence supporting a relationship between impulsivity and depression, as well as
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mania. Impulsivity could also be a component of the depressive state itself. Impulsivity appears
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differentially related to depressive and manic episodes. Swan and friends showed that both depression and mania is associated significantly to total and attentional impulsivity. Mania is associated to motor impulsivity while depression is associated to nonplanning impulsivity.
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Impulsivity is increased in bipolar disorder, even when patients are euthymic [20,21]. Euthymic bipolar patients express impulsivity at higher levels than healthy individuals [9], but they do not
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differ from manic bipolar patients [2]. These findings indicate that the impulsivity found among bipolar patients may be independent of mood state. Our findings confirming prior results of higher levels of impulsivity even patients are euthymic. Euthymic bipolar patients express higher total and subscale impulsivity scores. An association between impulsivity and bipolar disorder that extends across mood states is important because it would indicate that impulsivity is more than the direct
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expression of mood symptoms in the affected individuals. This association could have different origins: it could be a consequence of repeated mood episodes, a risk factor for the disorder, or a
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manifestation of an independent factor linked with the biological causes of the disorder. Each of these possibilities could have important implications for a better understanding of bipolar disorder.
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The role of impulsivity in substance abuse has recently received increased attention from both researchers and clinicians. Studies measuring impulsivity in substance-dependent individuals have
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also supported a link between impulsivity and substance abuse. Substance users are known to be highly impulsive and this is reflected in their BIS-11 scores. For instance, higher BIS-11 scores are found for cocaine dependent adults [13] and ecstasy users [14]. Early onset alcoholics score higher than on the late onset alcoholics [22]. Also among alcohol dependent patients, the number of cigarettes smoked correlates with the nonplanning subscale [23]. BIS-11 scores are predictive of the level of an individual's crack/cocaine use [24]. Most studies that use questionnaire measures of impulsivity find higher levels of impulsivity in substance-dependent individuals than in healthy comparison subjects [12,25,26]. Similarly those who are dependent on multiple substances are more impulsive than those who are dependent on single substances [27,28]. However the question of whether the higher level of impulsivity is a factor leading to or resulting from substance abuse has not been answered. Our findings confirming with the prior reports of increased impulsivity measures of substance use disorder. Substance abuse is prominent in bipolar disorder, and bipolar disorder may be equally common in substance abuse [29], bipolar disorder may be the most common non–substance-related Axis I
ACCEPTED MANUSCRIPT condition in patients with substance-related disorders [30,31]. Bipolar and substance-use disorders share common mechanisms, including impulsivity, poor modulation of motivation and responses to rewarding stimuli, and susceptibility to behavioral sensitization. Impulsivity is a core and pervasive feature of both BD and SUD [1] , and may provide a conceptual framework for understanding the
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high prevalence of comorbid BD and SUD and some manifestations of this comorbidity (e.g.
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aggressiveness, suicidality) [1,32]. Impulsivity may represent a risk factor for the development of SUD in BD patients, and/or a behavioral manifestation of a biological abnormality that predisposes to both disorders [33]. Cummulative increases in total BIS scores have been shown when substance
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abuse and BD are present simultaneously in patients [34]. These interesting results indicate a linkage between BD and the association between trait impulsivity and substance abuse.
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Four previous studies have examined trait impulsivity in BD patients with comorbid SUD [34, 35,36,37]. Results of all of them shows that BD patients with comorbid history of substance abuse or dependence was associated with higher BIS scores than isolated BD. However there is no any information about the difference of impulsivity measures between isolated BD and isolated SUD. One of the study a sample of 12 patients with BD comorbid with SUD, the presence of both
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diagnoses additively increased the total BIS scores [34] . Recently, it has been reported that BD patients with or without comorbid alcohol use disorder (AUD) differ from healthy comparison
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subjects on total and subscales of the BIS-11 [35] . However, the BD group comorbid with AUD and the BD group without comorbidity did not differ from each other on the attentional and
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nonplanning BIS-11 subscales, suggesting that only motor impulsivity is a particular characteristic of BD patients who develop AUD. In the another study, in a sample of 114 BD patients, a history of
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substance abuse or dependence was associated with higher BIS scores [36]. In another study fortyseven BD with comorbid AUD were compared to 66 BD alone and to 90 healthy controls. Alcoholic BD patients scored significantly higher than nonalcoholic BD and healty controls. On the total and on each subscale BIS scores [37]. Elevated levels of impulsivity is thought to be core and pervasive feature of both BD and substance use disorders. Maybe more impulsive individuals with bipolar disorder more susceptible to substance abuse [38,39,40]; or substance abuse itself could cause impulsivity to be increased in general, so bipolar disorder and substance abuse would be associated independently with increased impulsivity. But there is no any study that compare nature of impulsivity and impulsivity measures between isolated BD and SUD. In our study we found isolated BD and SUD both of them have increased total impulsivity, subscale attention and motor impulsivity did not differated; but on the nonplanning subscale BD patients are more impulsive than substance use disorder patient. Nonplannig impulsivity was higher in BP than substance use disorder. This refers to BD patients have special feature when they are
ACCEPTED MANUSCRIPT compared with SUD about impulsivity: lack of sense of future. To our knowledge this study is first to investigate the difference of impulsivity between isolated BD and SUD. We have few limitations. We used only one clinical measurement of impulsiveness and did not carry out cognitive assessment. The sample size is limited and patients are male because of the
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absence of female substance abuser patient in our clinic. Another limitation BD subjects in this
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study were all receiving psychotropic medicine despite being remission because of ethic issues. It is known that lithium, valproate and antipsychotics have antiimpulsive and antiaggressive effects [4149]. In our study it is important to note that despite the use of mood stabilizators and antipsychotics
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that reduce impulsivity, BD patients are more impulsive on the nonplanning impulsivity than SUD
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patients who take no medications. 5. Conclusion
Trait impulsivity was elevated in patients with isolated interepisode BD and SUD, confirming that impulsivity is relatively independent of mood state, and was higher in past substance users. Interepisode BD and substance use disorder patients have increased total impulsivity. On the
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nonplanning subscale male BD patients are more impulsive than male substance use disorder patients. Nonplannig impulsivity appeared to be related to bipolar disorder than substance use
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disorder. So these findings should be explored and replicated in larger samples.
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ACCEPTED MANUSCRIPT Table 1. Demographic and clinical characteristics of samples
BD (n = 35)
SUD (n=40)
Age,years
36,43 ± 14,08
29,65 ± 10,2
Age of onset BD
29,94 ± 13,07
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Characteristics
21,15 ± 5,4
Urban
31(88,6%)
29 (72,5%)
Rural
4 (11,4%)
11(27,5%)
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Age of onset SUD
Education (years)
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9,54 ± 3,8
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Location
Marital status
8,58 ± 2,6
15 (42,9%)
13(32,5%)
Single
19 (54,3%)
25 (62,5%)
Divorced
1 (2,9%)
2 (5%)
BD in first degree relatives
4 (11,4%)
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SUD in first degree relatives
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Married
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6 (15%)
ACCEPTED MANUSCRIPT Table 2. BIS-11A scores comparisons of diagnostic groups BD
SUD Mean(SD)
p value
Motor impulsivivty
19,80 (5,38)
20,20 (4,61)
0,74
Attentional impulsivity
26,03 (5,46)
24,80 (4,49)
0,21
Nonplanning impulsivity
17,03 (4,09)
15,15(3,66)
0,04*
Total impulsivity
63,34 (11,70)
60,85 (10,59)
0,32
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Mean(SD)
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BIS-11A = Barratt Impulsiveness Scale, version 11A; * p= 0,04; significant difference between BD
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and SUD on nonplanning impulsivity
S0010-440X(15)00020-6 doi: 10.1016/j.comppsych.2015.02.013 YCOMP 51485
To appear in:
Comprehensive Psychiatry
Received date: Revised date: Accepted date:
3 September 2014 11 February 2015 16 February 2015
Please cite this article as: Ozten Mustafa, Erol Atila, Karayılan Semra, Kapudan Hilal, Orsel Ertac Sertac, Kumsar Neslihan Akkisi, Impulsivity in Bipolar and Substance Use Disorders, Comprehensive Psychiatry (2015), doi: 10.1016/j.comppsych.2015.02.013
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Impulsivity in Bipolar and Substance Use Disorders
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Sakarya University, Faculty of Medicine, Department of Psychiatry, Sakarya, Turkey
Sakarya University Training and Research Hospital Psychiatry Clinic, Sakarya, Turkey
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Mustafa OZTEN, (Corresponding Author)
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b
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Akkisi Kumsarb
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Mustafa Oztena , Atila Erola, Semra Karayılana, Hilal Kapudana, Ertac Sertac Orsela, Neslihan
M.D. Sakarya University, Faculty of Medicine, Department of Psychiatry, Sakarya, Turkey Phone:
+905443727947
E-Mail: [email protected] Atila EROL,
Sakarya, Turkey
Semra KARAYILAN,
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E-Mail: [email protected]
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Professor of Psychiatry, Sakarya University, Faculty of Medicine, Department of Psychiatry,
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M.D. Sakarya University, Faculty of Medicine, Department of Psychiatry, Sakarya, Turkey E-Mail: [email protected] Hilal KAPUDAN,
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M.D. Sakarya University, Faculty of Medicine, Department of Psychiatry, Sakarya, Turkey E-Mail: [email protected] Ertac Sertac ORSEL,
M.D. Sakarya University, Faculty of Medicine, Department of Psychiatry, Sakarya, Turkey E-Mail: [email protected] Neslihan Akkisi KUMSAR, M.D. Sakarya University Training and Research Hospital Psychiatry Clinic, Sakarya, Turkey E-Mail: [email protected]
ACCEPTED MANUSCRIPT Impulsivity in Bipolar and Substance Use Disorders
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Abstract
Background: Bipolar disorder (BD) is commonly associated with increased impulsivity, particularly during manic and depressed episodes also impulsivity remains elevated during
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euthymic phases. Impulsivity is also a factor in the initiation and maintenance of substance use disorders (SUD). Impulsivity can predispose to substance abuse or can result from it. Impulsivity
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appears to be relatively independent of mood state and is higher in individuals with past substance use. So we wanted to compare in terms of impulsivity of BD and SUD closely associated with impulsivity and determine if any differences.
Methods: Impulsivity was evaluated by the Barratt Impulsiveness Scale (BIS-11A), in 35
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bipolar interepisode disorder male patients without any comorbid substance use disorder, 40 substance use disorder male patients. The BIS-11A mean scores for two groups were compared
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through one-way between-groups ANOVA.
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Results: There were no difference among the BD and substance use disorder on total and subscale attentional, motor impulsivity measures. However, for male patients there were difference on the nonplanning subscale. Male BD patient group scored higher than the male substance use
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disorder patient group for nonplanning impulsivity.
Conclusions: Our results replicate that interepisode BD and substance use disorder patients both have increased total impulsivity and extends them that trait impulsivity is not completely the same in subscales. Both groups were similar on attention and motor impulsivity subscales but on the nonplanning subscale BD patients are more impulsive than the substance use disorder patiens.
Keywords: Impulsivity; Bipolar disorder; Substance use disorder.
ACCEPTED MANUSCRIPT 1.Introduction Impulsivity is a disposition toward rapid, unplanned reactions to internal or external stimuli without regard to the negative consequences of these reactions to the self or to others [1] . Even though impulsivity is not itself a psychiatric diagnosis, it seems to be more common in some mental
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disorders such as certain personality disorders, bipolar disorders, impulse-control disorders (ICD)
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and substance abuse.
Impulsivity is a frequent component of the course and presentation of bipolar disorder; it has therefore been proposed to represent a core feature of the illness that persists across different
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affective states [1–8]. Among bipolar patients, impulsivity appears to be especially important during manic episodes, but may also be found during euthymia and other mood phases [1,2,9]. Both the
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impulsivity that appears in the manic phase of bipolar disorder (state impulsivity) and the stable impulsivity that may extend across mood states (trait impulsivity) are important features of bipolar disorder. Euthymic bipolar patients express trait impulsivity at higher levels than healthy individuals [9], but they do not differ from manic bipolar patients [3]. These findings indicate that the impulsivity found among bipolar patients may be independent of mood state.
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There is now widespread agreement that impulsivity plays a key role in the initiation and development of substance misuse problems. Impulsivity can predispose to substance abuse, and can
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result from it [10]. Substance users are known to be highly impulsive and this is reflected in their BIS-11 scores. Behavioral and rating scale measures of impulsivity are elevated in patients with
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substance abuse [11,12]. For instance increased impulsivity are found for cocaine dependent adults [13] and ecstasy users [14] relative to controls.
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Impulsivity, which is prominent in both bipolar disorder and substance abuse, may have behavioral and biological substrata that contribute to the overlap between the two disorders [1]. So in this study our goal was to compare impulsivity scores of patients with BD and SUD. Our hypothesis is BD and SUD have different impulsivity rates and profiles.
2. Methods
2.1 Participants 35 euthymic (interepisode) BD patients without any SUD and 40 euthymic SUD patients were recruited from the outpatient psychiatry clinic of Sakarya University Faculty of Medicine. BD and SUD diagnoses were obtained using the Structured Clinical Interview for DSM-IV diagnoses. Inclusion criteria were: (i) 18 years of age or older; (ii) diagnosis of euthymic BD without SUD comorbidity and SUD
ACCEPTED MANUSCRIPT without bipolar comorbidity; Exclusion criteria for all groups were: (i) presence of chronic illness (e.g., hypertension, diabetes, liver disease, kidney diseases, current thyroid dysfunction, or neurological disease); (ii) current comorbid Axis I disorders. All procedures were carried out after participants had demonstrated adequate understanding and provided written informed consent.
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For BD patients; diagnoses and mood state were verified with the Structural Clinical Interview
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for DSM-IV [15], the Hamilton Rating Scale for Depression, 21 items (HAM-D) [16], and the Young Mania Rating Scale (YMRS) [17]. Absence of mood symptoms at least one month before the interview, as well as scores of < 6 on the HAM-D and the YMRS scales, defined euthymia.
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SUD group were recruited from among patients applied by probation. Diagnosis of substance use disorder was made according to the Structured Clinical Interview for DSM-IV diagnoses. There
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was no substance use history, withdrawal symptom of substance and substance craving at least 3 months before the clinical interview. Patients were required to provide urine samples free of substances six times at intervals of 1 week. Urine samples were analyzed for cannabinoids and synthetic cannabinoids, cocaine, amphetamine, ecstasy, barbiturates, benzodiazepines, ethyl glucuronide, phencyclidine and opiates at our University Departmental Chemical Analysis
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Laboratory using the Enzyme Multiple Immunoassay Technique- Drug Abuse Urine assay. So they were not under the effect of any substance at their assessments. None of the SUD group were taking
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psychotropic medications for prophylaxis or anticraving at the time of assessment.
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2.2 Methods
Participants completed the Barratt Impulsiveness Scale version 11A (BIS- 11A) [18] to assess
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impulsivity. The BIS-11A is a 21-item self-report inventory that measures impulsivity as a trait encompassing three domains: attentional impulsivity (intolerance for complexity and persistence); motor impulsivity (tendency to act without forethought); and non-planning impulsivity (lack of a sense of the future). Items are rated from 1 (absent) to 4 (most extreme).
2.3 Statistical analysis All analyses were performed using the Statistical Package for the Social Sciences, version 16 for Windows (SPSS, Inc., Chicago, IL, USA). The two groups were compared using one-way betweengroups ANOVA. The level of significance was set at p = 0.05.
3. Results
3.1 Demographic Data 35 BD patients mean age 36,43 ± 14,08 and 40 SUD patients mean age 29,65 ± 10,2, age of
ACCEPTED MANUSCRIPT onset BD was 29,94 ± 13,07 and age of SUD was 21,15 ± 5,4, all patients was male. 31 BD and 29 SUD patients live in urban and 4 BD, 11 SUD patients live in rural area. The mean HAM-D score was 2.86±0.95, and the mean YMRS score was 1.91±0.76. Demographic and clinical characteristics of the 2 groups are displayed in table 1. Mean age of BP group was higher than the
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mean age of SUD group (t=2.40; DF=73; p=0.02).
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Table 1.
SUD group data show that 28 (%70) patients used cannabinoid and synthetic cannabinoid, 3 (%7,5) patients used ecstasy, 2 (%5) patients used heroine, 1 (%2,5) patient used cocaine. 6 (%15) patients used multiple substances. BD group were all receiving maintenance treatment. 27 (%77) of them were receiving lithium and mean dose was 900 mg/day. 12 (%34) lithium-treated patients also were receiving additional atypical antipsychotic treatment. Risperidone 3mg/day (mean dose), quetiapine 400 mg/day (mean dose) and olanzapine 10 mg/day (mean dose) was preferred. 8 (%23) of BD patients were receiving valproate and mean dose was 750 mg/day. 4 (%11) of valproate-treated patients also were receiving additional atypical antipsychotic medication. Risperidone 2 mg/day (mean dose) and quetiapine 300 mg/day (mean dose) were preferred.
ACCEPTED MANUSCRIPT 3.2 Group comparisons The BD and SUD groups scored similarly on total impulsivity measures (p>0.3) (Table 2 ). The BD and SUD groups did not differ regarding motor impulsivity (p>0.7) and attentional impulsivity (p>0.2). On the non-planning subscale there were difference among the BD and SUD; groups
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scored differently (p =0.04). Male BD patient group scored higher than the male substance use
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disorder patient group for nonplanning impulsivity; and this difference remains significant when the influence of age was controlled with ANCOVA.
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Table 2.
ACCEPTED MANUSCRIPT 4. Discussion Impulsivity is related to mechanisms and consequences of affective symptoms [1,19]. Impulsivity is
considered to be inherent in mania and is a prominent part of its diagnostic criteria [9,
15]. There is evidence supporting a relationship between impulsivity and depression, as well as
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mania. Impulsivity could also be a component of the depressive state itself. Impulsivity appears
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differentially related to depressive and manic episodes. Swan and friends showed that both depression and mania is associated significantly to total and attentional impulsivity. Mania is associated to motor impulsivity while depression is associated to nonplanning impulsivity.
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Impulsivity is increased in bipolar disorder, even when patients are euthymic [20,21]. Euthymic bipolar patients express impulsivity at higher levels than healthy individuals [9], but they do not
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differ from manic bipolar patients [2]. These findings indicate that the impulsivity found among bipolar patients may be independent of mood state. Our findings confirming prior results of higher levels of impulsivity even patients are euthymic. Euthymic bipolar patients express higher total and subscale impulsivity scores. An association between impulsivity and bipolar disorder that extends across mood states is important because it would indicate that impulsivity is more than the direct
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expression of mood symptoms in the affected individuals. This association could have different origins: it could be a consequence of repeated mood episodes, a risk factor for the disorder, or a
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manifestation of an independent factor linked with the biological causes of the disorder. Each of these possibilities could have important implications for a better understanding of bipolar disorder.
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The role of impulsivity in substance abuse has recently received increased attention from both researchers and clinicians. Studies measuring impulsivity in substance-dependent individuals have
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also supported a link between impulsivity and substance abuse. Substance users are known to be highly impulsive and this is reflected in their BIS-11 scores. For instance, higher BIS-11 scores are found for cocaine dependent adults [13] and ecstasy users [14]. Early onset alcoholics score higher than on the late onset alcoholics [22]. Also among alcohol dependent patients, the number of cigarettes smoked correlates with the nonplanning subscale [23]. BIS-11 scores are predictive of the level of an individual's crack/cocaine use [24]. Most studies that use questionnaire measures of impulsivity find higher levels of impulsivity in substance-dependent individuals than in healthy comparison subjects [12,25,26]. Similarly those who are dependent on multiple substances are more impulsive than those who are dependent on single substances [27,28]. However the question of whether the higher level of impulsivity is a factor leading to or resulting from substance abuse has not been answered. Our findings confirming with the prior reports of increased impulsivity measures of substance use disorder. Substance abuse is prominent in bipolar disorder, and bipolar disorder may be equally common in substance abuse [29], bipolar disorder may be the most common non–substance-related Axis I
ACCEPTED MANUSCRIPT condition in patients with substance-related disorders [30,31]. Bipolar and substance-use disorders share common mechanisms, including impulsivity, poor modulation of motivation and responses to rewarding stimuli, and susceptibility to behavioral sensitization. Impulsivity is a core and pervasive feature of both BD and SUD [1] , and may provide a conceptual framework for understanding the
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high prevalence of comorbid BD and SUD and some manifestations of this comorbidity (e.g.
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aggressiveness, suicidality) [1,32]. Impulsivity may represent a risk factor for the development of SUD in BD patients, and/or a behavioral manifestation of a biological abnormality that predisposes to both disorders [33]. Cummulative increases in total BIS scores have been shown when substance
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abuse and BD are present simultaneously in patients [34]. These interesting results indicate a linkage between BD and the association between trait impulsivity and substance abuse.
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Four previous studies have examined trait impulsivity in BD patients with comorbid SUD [34, 35,36,37]. Results of all of them shows that BD patients with comorbid history of substance abuse or dependence was associated with higher BIS scores than isolated BD. However there is no any information about the difference of impulsivity measures between isolated BD and isolated SUD. One of the study a sample of 12 patients with BD comorbid with SUD, the presence of both
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diagnoses additively increased the total BIS scores [34] . Recently, it has been reported that BD patients with or without comorbid alcohol use disorder (AUD) differ from healthy comparison
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subjects on total and subscales of the BIS-11 [35] . However, the BD group comorbid with AUD and the BD group without comorbidity did not differ from each other on the attentional and
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nonplanning BIS-11 subscales, suggesting that only motor impulsivity is a particular characteristic of BD patients who develop AUD. In the another study, in a sample of 114 BD patients, a history of
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substance abuse or dependence was associated with higher BIS scores [36]. In another study fortyseven BD with comorbid AUD were compared to 66 BD alone and to 90 healthy controls. Alcoholic BD patients scored significantly higher than nonalcoholic BD and healty controls. On the total and on each subscale BIS scores [37]. Elevated levels of impulsivity is thought to be core and pervasive feature of both BD and substance use disorders. Maybe more impulsive individuals with bipolar disorder more susceptible to substance abuse [38,39,40]; or substance abuse itself could cause impulsivity to be increased in general, so bipolar disorder and substance abuse would be associated independently with increased impulsivity. But there is no any study that compare nature of impulsivity and impulsivity measures between isolated BD and SUD. In our study we found isolated BD and SUD both of them have increased total impulsivity, subscale attention and motor impulsivity did not differated; but on the nonplanning subscale BD patients are more impulsive than substance use disorder patient. Nonplannig impulsivity was higher in BP than substance use disorder. This refers to BD patients have special feature when they are
ACCEPTED MANUSCRIPT compared with SUD about impulsivity: lack of sense of future. To our knowledge this study is first to investigate the difference of impulsivity between isolated BD and SUD. We have few limitations. We used only one clinical measurement of impulsiveness and did not carry out cognitive assessment. The sample size is limited and patients are male because of the
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absence of female substance abuser patient in our clinic. Another limitation BD subjects in this
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study were all receiving psychotropic medicine despite being remission because of ethic issues. It is known that lithium, valproate and antipsychotics have antiimpulsive and antiaggressive effects [4149]. In our study it is important to note that despite the use of mood stabilizators and antipsychotics
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that reduce impulsivity, BD patients are more impulsive on the nonplanning impulsivity than SUD
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patients who take no medications. 5. Conclusion
Trait impulsivity was elevated in patients with isolated interepisode BD and SUD, confirming that impulsivity is relatively independent of mood state, and was higher in past substance users. Interepisode BD and substance use disorder patients have increased total impulsivity. On the
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nonplanning subscale male BD patients are more impulsive than male substance use disorder patients. Nonplannig impulsivity appeared to be related to bipolar disorder than substance use
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disorder. So these findings should be explored and replicated in larger samples.
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ACCEPTED MANUSCRIPT Table 1. Demographic and clinical characteristics of samples
BD (n = 35)
SUD (n=40)
Age,years
36,43 ± 14,08
29,65 ± 10,2
Age of onset BD
29,94 ± 13,07
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Characteristics
21,15 ± 5,4
Urban
31(88,6%)
29 (72,5%)
Rural
4 (11,4%)
11(27,5%)
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Age of onset SUD
Education (years)
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9,54 ± 3,8
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Location
Marital status
8,58 ± 2,6
15 (42,9%)
13(32,5%)
Single
19 (54,3%)
25 (62,5%)
Divorced
1 (2,9%)
2 (5%)
BD in first degree relatives
4 (11,4%)
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SUD in first degree relatives
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Married
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6 (15%)
ACCEPTED MANUSCRIPT Table 2. BIS-11A scores comparisons of diagnostic groups BD
SUD Mean(SD)
p value
Motor impulsivivty
19,80 (5,38)
20,20 (4,61)
0,74
Attentional impulsivity
26,03 (5,46)
24,80 (4,49)
0,21
Nonplanning impulsivity
17,03 (4,09)
15,15(3,66)
0,04*
Total impulsivity
63,34 (11,70)
60,85 (10,59)
0,32
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Mean(SD)
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BIS-11A = Barratt Impulsiveness Scale, version 11A; * p= 0,04; significant difference between BD
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and SUD on nonplanning impulsivity
