The impact of intolerance of uncertainty, worry and irritability on quality of life in persons with epilepsy: irritability as mediator

Accepted Manuscript

Title: The impact of intolerance of uncertainty, worry andirritability on quality of life in persons with epilepsy:irritability as mediator

Author: Usha Barahmand Afsar Haji

PII: S0920-1211(14)00194-6DOI: http://dx.doi.org/doi:10.1016/j.eplepsyres.2014.07.002Reference: EPIRES 5186

To appear in: Epilepsy Research

Received date: 7-4-2014Revised date: 6-7-2014Accepted date: 14-7-2014

Please cite this article as: Barahmand, U., Haji, A.,The impact ofintolerance of uncertainty, worry and irritability on quality of life inpersons with epilepsy: irritability as mediator, Epilepsy Research (2014),http://dx.doi.org/10.1016/j.eplepsyres.2014.07.002

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 proofbefore it is published in its final form. Please note that during the production processerrors may be discovered which could affect the content, and all legal disclaimers thatapply to the journal pertain.

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Title: The impact of intolerance of uncertainty, worry and irritability on quality of life in persons with epilepsy: irritability as mediator

Running head: Irritability in QoL of PWE

Authors

Name: Usha Barahmand

Designation: Associate professor

Affiliation: University of Mohaghegh Ardabili, Ardabil, Iran

Email: [email protected]

[email protected]

Name: Afsar Haji

Affiliation: University of Mohaghegh Ardabili, Ardabil, Iran

Email: [email protected]

Corresponding author

Name: Usha Barahmand

Designation: Associate professor

Affiliation: University of Mohaghegh Ardabili, Ardabil, Iran

Email: [email protected]

Cell: +98 914 451 9649

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The impact of intolerance of uncertainty, worry and irritability on quality of life in persons with epilepsy: irritability as a mediator

Abstract

Epilepsy is a neurological disorder afflicting many people in the world. The impact of epilepsy on the quality of life of those afflicted with epilepsy is greater than the limitations imposed by the seizures alone. Among the several psychological disorders found to be comorbid with epilepsy are anxiety and depression, both of which impair quality of life in epilepsy. Some studies have reported that the anxiety seen in epilepsy is characterized by worry while the depression seen is characterized by irritability. A concept common to both anxiety and depression is intolerance of uncertainty. Therefore, the study explores the relationship between intolerance of uncertainty, worry and irritability and their association to quality of life in epilepsy. A descriptive-correlational research method was used and the research sample comprised 60 consecutive referrals seeking outpatient neurological services for epilepsy at Alavi Hospital in Ardebil. Data were collected by administering the Penn State Worry Questionnaire, Intolerance of Uncertainty Scale, Irritability Questionnaire and Quality of Life in Epilepsy Inventory. Data were analyzed using Pearson’s correlation coefficients and multivariate regression analysis. Mediation and moderation analyses were conducted. Findings indicated that intolerance of uncertainty, worry and irritability have unique significant effects on quality of life. The implications are that interventions aimed at improving the quality of life of patients with epilepsy should address their feelings of uncertainty, worry and irritability. Furthermore, irritability seems to mediate the impact of both intolerance of uncertainty and worry on quality of life of individuals with epilepsy. No significant moderation effects were noted. Results underscore the important role of irritability in the quality of life of persons with epilepsy. The findings are discussed with reference to the possibility of particular predisposing temperaments and add credence to the suggestion of an epileptic personality.

Keywords: worry; uncertainty; irritability; quality of life, epilepsy

Epilepsy is a chronic neurological disorder that imposes a severe burden on afflicted individuals(Wiebe, Bellhouse, Fallahay, Eliasziw, 1999) and affects their functional status (Meldolesi, Di Gennaro, Quarato, Esposito, Grammaldo, Morosini, Cascavilla, & Picardi. (2007). Persons with epilepsy (PWE) usually suffer from several negative social consequences such as unemployment and/or underemployment, lower marriage rates, and social discrimination, all of which coupled with the seizures themselves usually result in an impaired quality of life (QoL) (Aydemir, Ozkara, Unsal, & Canbeyli, 2011). .

Epilepsy is often associated with various somatic, psychiatric, and neurodevelopmental conditions which can affect the QoL of PWE and reduce their rehabilitation efficacy potential (Selassie, Wilson, Martz, Smith, Wagner, & Wannamaker, 2014). Furthermore, epilepsy is also associated with an increased risk for psychopathology, the most frequent disorders being

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depression, seen in as many as 44%‐63% of patients with epilepsy (Barry, 2003; Harden, 2002;

Hermann, Seidenberg, Bell, 2000; Szaflarski & Szaflarski, 2004; Zhao, T., Sun, M., Yu, P., Zhu,

G., Tang, X., Shi, Y., & Hong, 2012) , and anxiety, reported in about 5%‐32% of individuals

with epilepsy (Choi-Kwon S, Chung C, Kim H, et al., 2003; Vazquez and Devinsky, 2003). The severity of both depression and anxiety have been reported to impact quality of life (Huang, Che, Liu, Jiang, & Mao, 2011).

Although depression is the most common comorbid psychiatric condition in PWE, its clinical manifestation is often atypical with the symptoms of irritability and anxiety (Kanner, 2013). Irritability has been defined as the ‘tendency to react impulsively, controversially, or rudely at the slightest provocation or disagreement’ Caprara, Cinanni, D’Imperio, Passerini, Renzi, Travaglia, 1985), ‘a readiness to explode with negative affect at the slightest provocation, including quick temper, grouchiness, exasperation, and rudeness’ (Buss and Durkee, 1957), as a mood that predisposes towards certain emotions (e.g. anger), certain cognitions (e.g. hostile appraisals) and certain actions (e.g. aggression), (Craig, Hietanen, Markova, & Berrios, 2008), and more recently, as a mood of easy annoyance and touchiness characterized by anger and temper outbursts (Stringaris, 2011). It is subjectively unpleasant and objectively characterized by expressions of negative emotion in interpersonal relationships (Craig, et al., 2008).

Irritability is a common clinical problem in patients with neuropsychiatric disorders such as Huntington's disease, traumatic brain injury, dementias, and Parkinson's disease (Craig et al., 2008). Blumer (2004) has developed the term interictal dysphoric disorder, which he views as a ‘‘subictal variation’’whose essential clinical attribute is ‘‘paroxysmal affects’’ ranging from irritability to anger to rage. Irritability is a major source of distress to patients and their carers, can lead to social and family dysfunction, and remains one of the main factors responsible for patient hospitalization and institutionalization. Studies have linked irritability and hostility to other aspects of morbidity including treatment non-adherence (Pugh, 1983), suicide attempts (Horesh, Rolnick, Iancu, Dannon, Lepkifker, Apter, Kotler, 1997; Akiskal, Benazzi, Perugi, Rihmer, 2005) and violence (Asnis, Kaplan, van Praag, Sanderson., 1994). Aggression theorists agree that irritability is a precursor of affective/emotional aggression (Berkowitz, & Harmon-Jones 1993; Geen, 2001; Caprara, Cinanni, D’Imperio, Passerini, Renzi, Travaglia, 1985).

Clinical interest in youth irritability has been growing in recent years (Stringaris, 2011). Although it has long been a criterion of several psychiatric disorders and recently been added as a defining characteristic of disruptive mood dysregulation disorder in DSM-5 (American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 2013), irritability in youth remains largely understudied (Leibenluft, 2011).

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Some studies have identified irritability as a risk factor for later psychopathology, specifically depressive and anxiety disorders (Copeland, Shanahan, Costello, Angold, 2009; Mulraney, Quek, Whelan, Tonge, Melvin, 2012; Stringaris, Cohen, Pine, & Leibenluft, 2009; Stringaris, Zavos, Leibenluft, Maughan, & Eley, 2012). Some studies suggest a possible link between irritability and later development of bipolar disorder and other diagnoses (Fergus, Miller, Luckenbaugh, 2003; Kim-Cohen, Caspi, Moffitt, Harrington, Milne, Poulton, 2003), while others have found irritability associated with alcohol related aggression (Giancola, 2002), significant impairment (Stringaris, & Goodman, 2009), lower income and educational achievement (Stringaris, Cohen, Pine, Leibenluft, 2009) in individuals without a psychiatric disorder. Irritability has even been reported to be common among nondepressed medical patients, and, therefore, considered a normal psychological reaction to illness, unless persistent or severe (Clark, Cavanaugh, & Gibbons, 1983). That is, irritability may be indicative of a reactive mood instability due to transient pathological conditions. Given the above observations, the importance of irritability in PWE is obvious.

Interictal anxiety presents as feelings of worry or as a formal anxiety disorder, such as panic disorder, obsessive-compulsive disorder, or generalised anxiety disorder (GAD) (Meldolesi, et al., 2007). Seizure frequency has been linked with severity of anxiety in some studies (Jacoby, Baker, Steen, Potts, & Chadwick, 1996), and symptoms of depression and seizure worry have been found to be the most important factors affecting QoL (Loring, Meador, & Lee, 2004).

Worry is a thought activity characterized by a predominance of anxious predictions about possible future negative events (Borkovec, 1994). Worry is considered a good indicator of the severity of anxiety. Therefore, assessments of worry can be used as a proxy for the presence and severity of anxiety (Norton, Sexton, Walker, & Norton, 2005).

One concept within anxiety psychopathology that has been linked to the development and continuation of problematic worry ((Buhr, & Dugas, 2006; Laugesen, Dugas, & Bukowski, 2003; Robichaud, Dugas, & Conway, 2003; van der Heiden, Melchior, Muris, Bouwmeester, Bos, & van der Molen, 2010) is intolerance of uncertainty. Intolerance of uncertainty has been defined as a tendency to react negatively on an emotional, cognitive, and behavioral level to uncertain situations and events (Dugas, Buhr, & Ladouceur, 2004; Dugas & Robichaud, 2007) resulting in biased information processing and faulty appraisals of heightened threat and reduced coping (McEvoy, & Mahoney, 2013). Research has demonstrated that IU is the most salient predictor of worry (Laugesen, et al., 2003; Robichaud, et al., 2003; van der Heiden, et al., 2010). Furthermore, changes in IU have been shown to precede changes in level of worry, over the course of treatment, implying that IU may be a casual risk factor for heightened levels of worry. (Ladouceur, Gosselin, & Dugas, 2000). Since worry regarding various issues such as seizures, medication effects, and independent functioning have been reported in PWE, it seems likely that IU may have a role to play.

More recently, elevated IU has been associated with OCD (Holaway, Heimberg, Coles, 2006; Lind & Boschen, 2009; Tolin, Abramowitz, Brigidi & Foa, 2003), social anxiety (Boelen & Reijntjes, 2009; Carleton, Collimore, & Asmundson, 2010; Norton, Sexton, Walker & Norton, 2005; van der Heiden et al., 2010), panic disorder (Buhr & Dugas, 2009; Carleton, Sharpe, &

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Asmundson, 2007).There is also substantial evidence of an association between IU and depression (Boelen, Vrinssen, & van Tulder, 2010; Butzer & Kuiper, 2006; McEvoy and Mahoney, 2011; Miranda, Fontes, & Marroquin, 2008; Norton & Mehta, 2007; Norton et al.,2005; van der Heiden et al., 2010; Yook, Kim, Suh, & Lee, 2010). Therefore, research findings seem to suggest that IU is not specific to worry and anxiety, but rather is a transdiagnostic vulnerability factor (Carleton, Mulvogue, Thibodeau, McCabe, Antony, Asmundson, 2012).

As both anxiety and depression are highly comorbid in PWE, and since irritability and IU asdispositional characteristics may be a vulnerability factor to both, the investigation of irritability and IU in PWE is warranted. The present study aimed to examine the association of irritability, intolerance of uncertainty and worry to the quality of life of patients with epilepsy.

In order to illustrate whether there are mediation and/or moderation effects, we first focus our attention to worry and then irritability as mediators of the different variables in their relation to quality of life. Secondly, we use all the variables to find which of these variables moderate the effects on quality of life.

The specific aims of the present study were:

1. To investigate if worry mediated the effect of intolerance of uncertainty and irritability on

QoL.

2. To investigate if irritability mediated the effect of intolerance of uncertainty and worry on

QoL.

3. To examine moderation effects between irritability, intolerance of uncertainty and worry

on QoL.

Method

Ethics statement

This research protocol was approved by the Ethics Committee of the University of Mohaghegh Ardabili, Iran, and written informed consent was obtained from the study participants prior to administration of the questionnaires.

Participants

Participants were recruited from the neuropsychiatry outpatient services of Alavi Hospital in Ardabil, Iran. The registry maintained at the hospital shows that in the past one year, a total of 70 patients with epilepsy sought medical services repeatedly. Considering this figure as the size of the population, and with a 95% confidence level and .05 precision, the sample size required was calculated to be 60 using Yamane’s (1967) formula. The study sample comprised 60consecutive referrals (males = 28, females = 32) over the age of 18 years with a confident

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diagnosis of epilepsy. The final sample ranged in age from 19 to 51, with the mean age of the participants being 33.13 years (SD = 12.39).

Measures

Quality of Life in Epilepsy Inventory (QOLIE-31; (Cramer, Perrine, Devinsky, Bryant-Comstock, Meador, Hermann, 1998)

The QOLIE-31 is a questionnaire to assess health-related quality-of-life (HRQOL) in people with epilepsy. The QOLIE-31 is a 31-item questionnaire comprising seven subscales covering general and epilepsy-specific domains. The questionnaire contains seven multi-item scales that tap the following health concepts: seizure worry, overall quality of life, emotional well-being, energy fatigue, cognitive functioning, medication effects and social functioning. The subscales are grouped into two factors: Emotional/Psychological Effects (seizure worry, overall QOL, emotional well-being, energy/fatigue subscales) and Medical/Social Effects (medication effects, work-driving-social limits, cognitive function subscales). The scoring procedure for the QOLIE-31 converts the raw precoded numeric values of items, having scores of 0-100 where higher scores reflect a better quality of life. An overall score is obtained by using a weighted average of the multi-item scale scores (Vickrey, Perrine & Hays, 1993). Subscale and total scores can be calculated. During development, internal consistency reliability coefficients (Cronbach’s alpha)ranged from α = 0.77 (social functioning scale) to α = 0.85 (cognitive functioning scale). Test-retest data demonstrated good reliability (range r=0.64-0.85).

In the present study, the Persian version of the questionnaire was used and internal consistency coefficient for the total score was .92, with subscale α coefficients of .83 (seizure worry), .76 (overall quality of life), .73 (emotional well-being), .71 (energy/fatigue), .92 (Cognitive), .70 (medication effect) and .71 (social function).

Irritability Questionnaire (IRQ; Craig, Hietanen, Markova, & Berrios, 2008)

The IRQ was designed to capture cognitive and emotional aspects of irritability that are unpleasant. This clinical scale includes items relating to irritability based on cognition and appraisal theory (e.g. I feel as if people make my life difficult on purpose), subjective awareness and labelling of irritable feelings (e.g. I have been feeling like a bomb, ready to explode) and the behavioural expression of irritable mood (e.g. I lose my temper and shout or snap at others) (Craig et al., 2008).The IRQ is a 21-item self-rated, Likert scaled questionnaire for completion by patients. Patients are asked to indicate how often and how much in the past two weeks they have had the experience described by each statement using a 4-point scale ranging from 0 = never/not at all to 3 = most of the time/very much. Two subscale scores (frequency and severity) as well as a global score can be obtained. Subscale scores range from 0 to 63. In this study the average of the two subscale scores were used as the total score of irritability. The psychometric properties of the original scale have been reported to be desirable (Craig et al., 2008). In the

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present study, the Persian version of this questionnaire revealed an internal consistency of .87 for the global score and .88 and .90 for the frequency and severity subscales, respectively.

The Intolerance of Uncertainty Scale (IUS; Freeston, Rheaume, Letarte, Dugas, & Ladouceur, 1994)

The Intolerance of Uncertainty Scale was designed to measure an individual’s negative beliefs about and reactions to uncertainty. The scale consists of 27 items and is scored on a 1 (‘‘not at all characteristic of me’’) to 5 (‘‘entirely characteristic of me’’) Likert-type scale. Total scores range from 27 to 135. Excellent internal consistency (α =.94), and good test–retest reliability over a 5-week period (r = .74) have been reported (Buhr & Dugas, 2002). Recently, Sexton and Dugas (2009) reported two kinds of beliefs underlying the IUS: Uncertainty Has Negative Behavioral and Self-Referent Implications (Factor 1; α = .89) and Uncertainty Is Unfair and Spoils Everything

(Factor 2; a = .87). The present study has demonstrated excellent internal consistency for this scale (total scale α = .95; Factor 1 α = .90; Factor 2 α = .91). In the current study, the total scorewas used due to the absence of any a priori hypotheses relating to each subscale.

The Penn State Worry Questionnaire (PSWQ; Meyer, Miller, Metzger, & Borkovec, 1990)

The Penn State Worry Questionnaire is a measure of worry phenomena. The PSWQ has 16 items and was designed to capture the generality, excessiveness, and uncontrollability dimensions of pathological worry. Each item is rated on a scale from 1 (‘not at all typical of me’) to 5 (‘very typical of me’). Eleven items are worded in the direction of pathological worry, (e.g. I am always worrying about something) and high scores on these items indicate more worry. The other five items are worded so as to indicate that worry is not a problem, (e.g. I find it easy to dismiss worrisome thoughts), and low scores on these are indicative of worry. Total score is calculated by first reversing the scores of the latter group of five items and then summing scores on all the 16 items. Total scores range between 16 and 80, with higher scores indicating greater pathological worry. The PSWQ has shown to possess high internal consistency and good test-retest reliability (Meyer et al., 1990). In the present sample, the coefficient alpha for the total score was 0.91, indicating excellent internal consistency for the Persian version of this questionnaire.

Procedure

Before responding to the questionnaires, all participants were first informed about the purpose of the study, ensured complete anonymity and informed that they could end their participation whenever they liked. After they gave written consent to participation, the questionnaires were administered individually.

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Results

Sample characteristics

The socio-demographic and clinical characteristics of the participants are displayed in Table 1.

Correlational analysis

QoL showed negative, significant relationships with worry, irritability and intolerance of uncertainty. Table 2 presents the correlation coefficients, mean values and standard deviations (SD), as well as Cronbach’s α for all the variables in the study.

Mediation analysis

Regression analyses were performed in order to investigate if worry mediated the effect of intolerance of uncertainty and irritability on quality of life (aim 1). The first regression showed that intolerance of uncertainty (B = -.150, 95% CI [-.27, -.02], β = -.38, t = -2.46, p =.019), and irritability (B = -.714, 95% CI [- 1.01, -.42], β = -.82, t = -4.88, p = .000) each had a unique effect on quality of life.

The second regression tested whether intolerance of uncertainty and irritability uniquely predicted the mediator (i.e., worry). Intolerance of uncertainty (B= .22, 95% CI [.09, .35], β = .47, t = 3.53, p = .001), and irritability were found to be positively associated (B = .68, 95% CI [.41, .95], β = .68, t = 5.10, p = .000) to worry.

A hierarchical regression analysis using quality of life as the outcome variable was performed using intolerance of uncertainty and irritability as predictors in the first step, and worry as predictor in the second step. This analysis allows the examination of whether intolerance of uncertainty and irritability predict quality of life and if this relation is weakened in the presence of worry as the mediator. The result indicated that together both intolerance of uncertainty and irritability predicted quality of life significantly, but the contribution of intolerance of uncertainty (B = .066, 95% CI [.07, .20], β = .16, t = .977, p = .336) was insignificant while that of irritability remained significant (B = -.71, 95% CI [-1.01, -.41], β = -.81, t = -4.80, p = .000). When worry (i.e., the mediator) was controlled predictability was insignificant for intolerance of uncertainty (B= .067, 95% CI [-.07, .21], β = .17, t = .972, p = .338) but still significant for irritability (B = -.729, 95% CI [-1.14, -.32], β = -.83, t = -3.64, p = .001). Worry, as a hypothesized mediator, failed to predict quality of life when both intolerance of uncertainty and irritability were controlled for (B= .022, 95% CI [-.31, .35], β = .03, t = .138, p =.891). These results indicate that that while worry does mediate the relationship between intolerance of uncertainty and quality of life, it does not act as a mediator in the relationship between irritability and quality of life. See Table 3 for details.

A Sobel test was conducted to test the mediating criteria and to assess whether indirect effects were significant or not. The result showed that the complete pathway from intolerance of uncertainty (independent variable) to worry (mediator) to quality of life (dependent variable) was significant (z = -2.27, p =.02). However, the complete pathway from irritability (independent

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variable) to worry (mediator) to quality of life (dependent variable) was not significant (z = -0.67, p =.50). Thus, indicating that worry mediates the effects of intolerance of uncertainty but not that of irritability on quality of life. These results indicate that while irritability contributesdirectly to explain the variation in quality of life but intolerance of uncertainty contributes indirectly via experienced level of worry (see Figure 1).

For the second aim, regression analyses were performed in order to test if irritability mediated the effect of intolerance of uncertainty, and worry on quality of life. The first regression showed that intolerance of uncertainty (B= -.156, 95% CI [-.274, -.04], β = -.413, t= -2.76, p = .009), and worry (B= -.364, 95% CI [-.62 -.11], β = -.44, t = -2.94, p =.006), predicted quality of life independently of each other.

The second regression investigated if intolerance of uncertainty and worry uniquely predicted the mediator (i.e., irritability). Irritability was positively associated to both intolerance of uncertainty (B = .296, 95% CI [.18, .41], β = .62, t = 5.23, p =.000), and worry (B =.546, 95% CI [.33, .76], β = .54, t = 5.11, p = .000).

A hierarchical regression analysis using quality of life as the outcome and intolerance of uncertainty and worry as the predictors in the first step, and irritability as the predictor in the second step, allowed the examination of whether intolerance of uncertainty and worry anxietypredicted quality of life and if this association would weaken when irritability (i.e., the mediator) was present. In the first step of the regression worry (B = -.364, 95% CI [-.62, -.11], β = -.44, t = -2.94, p =.006) but not intolerance of uncertainty (B = -.084, 95% CI [-.20, .03], β = -.22, t = -1.47, p = .150) significantly explained quality of life. When irritability (i.e., the mediator) was controlled for, predictability was insignificant for both intolerance of uncertainty (B = .067, 95% CI [-.07, .21], β= .17, t = .972, p = .338) and worry (B = .022, 95% CI [-.31, .35], β = .03, t =.138, p =..891). In the second step, the mediator (i.e., irritability) predicted quality of life even when intolerance of uncertainty and worry were controlled for (B = -.729, 95% CI [-1.14, -.32], β = -.83, t = -3.64, p = .001). Irritability improved the prediction of quality of life over-and-above the independent variables (i.e., intolerance of uncertainty and worry). See Table 4 for the details.

Furthermore, the Sobel test indicated that the complete pathways from the independent variables (intolerance of uncertainty: z =-3.62, p= .000; worry: z = -2.94, p = .003) to the mediator (i.e., irritability), to the outcome (i.e., quality of life) were significant. These specific results might be explained on the basis that irritability completely mediated the effects of both intolerance of uncertainty and worry on quality of life. In other words, worry contributed directly to explain the variation in quality of life and indirectly via the experienced level of irritability. Intolerance of uncertainty contributed only indirectly via the experienced level of irritability to explain the variation in depression. In other words, irritability effects on quality of life originate from ‘‘its own power’’ and explained more of the variation in quality of life than intolerance of uncertainty (see Figure 2).

Moderation analysis

Multiple linear regression analyses were used in order to examine moderation effects between intolerance of uncertainty, worry, irritability and quality of life. The analysis indicated that about

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45.4% of the variation in the dependent variable (i.e., quality of life) could be explained by the main effects but the interaction effects failed to contribute to the variance (R2 = .50, adjusted R2

=.454, F (1, 57) = 13.26, p = .001). When the variables (dependent and independent) were standardized, both the standardized regression coefficients beta (b) and the unstandardizedregression coefficients beta (B) became the same value with regard to the main effects. All three of the main effects were significant and contributed uniquely to low levels of quality of life:intolerance of uncertainty (B = -.156, t = -2.47, p = .019), worry (B = -.368, t = -2.58,

p =.015), and irritability (B = -.729, t = -3.64, p =.001). Furthermore, the results indicated that none of the moderator effects were significant. That is the interactions between intolerance of uncertainty, worry and irritability failed to contribute to the predictability of these variables in isolation. (see Figure 3).

Discussion

The results in the present study show that (i) worry partially mediated the effects of intolerance of uncertainty, (ii) worry did not mediate the effects of irritability on quality of life, (ii) that irritability completely mediated the effects of both intolerance of uncertainty and worry on quality of life, (iii) there were no significant interaction effects between intolerance of uncertainty, worry and irritability on quality of life.

Mediating effects

The study suggests that worry contributes directly to explaining the variance in quality of life while intolerance of uncertainty might contribute both directly to explaining the variance in quality of life of PWE, and indirectly by increasing their feelings of worry. Indeed, PWE who experience uncertainty over a long period of time are susceptible to increased worry and lower quality of life. Uncertainty about the unpredictability of seizures, stigma, autonomy and the future have all been found to have significant impacts for PWE (De Boer, Mula, Sander, 2008;Kerr, Nixon, & Angalakuditi, 2011). Irritability contributed only directly to low quality of life.Irritability is a relatively common phenomenon in PWE, and is a symptom that is frequently seen as part of a depressive disorder in PWE (Alper, Barry, & Balabanov, 2002). Irritability has been described as one of the key symptoms of interictal dysphoric disorder and found to be significantly related to depressive mood (Taycan, & Taycan, 2014). Inasmuch as irritability is related to depression, it is likely to make PWE susceptible to lowered quality of life.

Previous research has documented that in general, irritability in PWE may result in peri-ictical aggression, underscoring the importance of irritability control in PWE (see Dinkelacker, Dietl, Widman, Lengler, & Elger, 2003). The study also showed that irritability completely mediated the effects of intolerance of uncertainty and worry on quality of life. Intolerance of uncertainty and worry contributed directly to explain the variation in quality of life, and indirectly through the experienced level of irritability. Irritability affects the quality of life PWE on the basis of ‘its own power’ and explains much more of the variation in depressive experiences than worry or intolerance of uncertainty.

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In addition, PWE who experience intolerance of uncertainty are very likely to also experienceworry, which may then become a source of irritability further lowering their quality of life. Worry about seizures (Wua, Ding, Wang, & Hong, 2010; Harden, et al., 2007; Pauli, de Oliveira Thais, Claudino, Bicalho, Bastos, Guarnieri, Nunes, Lin, Linhares, & Walz, 2012;) medication effects (Richardson, Farias, Lima III, & Alsaadi , 2004), health (Hessen, Lossius, & Gjerstad, 2009) or stigma (Orozco, 2005), for instance, may increase the risk for experiencing lower quality of life among PWE.

Moderator effects/interaction effects

The present study showed that the interaction between intolerance of uncertainty, worry and irritability did not influence self-reported quality of life. Absence of moderation effects among intolerance of uncertainty, worry and irritability imply that PWE experiencing high levels of intolerance of uncertainty are also likely to report high levels of worry and irritability. This finding confirms earlier findings that underline the strong positive association between anxiety(indexed by worry) and depression (indexed by irritability) in PWE (Barry, et al., 2008;Beyenburg, Mitchell, Schmidt, Elger, Reuber, 2005; Huang, et al., 2011; Kanner, 2009). A recent study (Maroufi, A., Khomand, P., Ahmadiani, S., Shams Alizadeh, N. & Gharibi, 2014) found high rates of both state and trait anxiety in PWE, implying that anxiety in epilepsy may be indicative of genetic or temperamental factors. Another recent study (Taycan & Taycan, 2014) has also suggested the possibility of an irritable or anxious temperament in PWE. The results of the present study fit these previous observations and point to the importance of irritability in affecting the life satisfaction and well-being of PWE.

The findings from this study need to consider certain limitations. For one thing, the findings are based on a sample from one province. Although the patients were recruited from the only center that caters to the needs of PWE of the whole province, replications with larger representative samples and studies with a community-based design should be conducted to determine a relatively realistic description of quality of life in patients with epilepsy and to confirm the findings of this study. Several clinical correlates of QoL such as duration of illness, comorbid conditions and number of drugs taken were not controlled and may have impacted the variables studied. Even so, they might have an impact on QoL or on each of the variables, but the findings from the mediation and moderation analyses pertaining to intolerance of uncertainty, worry and irritability may still hold. Other psychosocial variables such as stigma and self-efficacy may impact QoL and incorporating them along with irritability may reveal a clearer picture of the variables amenable to intervention aimed at QoL improvement.

The strength of the study lies in it being the first to focus on the role of irritability in epilepsy. The results of this study open up a number of avenues for future research. The validity of these findings can be evaluated in future work with epilepsy patients of different ages, which can also investigate the association of clinical and psychosocial variables to irritability. This study was a

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first step and more extended studies may help validate the concepts of anxious and irritable temperaments in epilepsy.

References

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Table 1

Showing the socio-demographic and clinical characteristics of the sample

Frequency Percent

Gender Female 32 53.3Male 28 46.7

Marital status Single 33 55Married 27 45

Age 19-25 years 20 33.326-30 years 12 2031-35 years 10 16.736-40 years 7 11.740 11 18.33

Type of seizure Tonic 7 11.66Tonic-Clonic 53 88.33

Number of drugs prescribed 1 3 52 18 303 21 354 14 23.35 4 5

With comorbid somatic conditions

40 66.7

Total 60 100

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Table 2

Correlation coefficients, mean values and standard deviations (SD), as well as Cronbach’s α for

all the variables in the study

gender age

Type of seizure QoL worry irritability IU

gender 1age .009 1

Seizure type .063 .067 1QoL .188 -.346* .078 1

worry -.359** .124 -.171 -.562** 1

irritability -.329* .215 .006 -.681** .644** 1IU -.103 .091 .136 -.438** .462** .622** 1

Mean & SD-

33.13±12.39

-50.71±7.8

758.77±11.3

638.69±9.60

82.72±20.97

Cronbach’s α

- - - .92 .91 .87 .95

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Table 3. Predictors for quality of life using worry as the mediator.

Predictors Step 1 Step 2B B

Intolerance of uncertainty .066 .067Irritability -.711*** -.729***Worry .022R2 .501 .501F 16.55*** 10.71***ΔR2 .000ΔF .019** p < .01; *** p < .001

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Table 4 Predictors for quality of life using irritability as the mediator.

Predictors Step 1 Step 2B B

Intolerance of uncertainty -.084 .067Worry -.368** .022Irritability -.729R2 .294 .501F 6.88** 10.71***ΔR2 .207ΔF 13.26***** p < .01; *** p < .001

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B = .22*** B = .022

B = .68

B = -.150** B = .067

B = -.714*** B = -.729***

Figure 1. Mediation model showing that the effect of intolerance of uncertainty and irritability

(independent variables) on quality of life (outcome) is not mediated by worry (mediator).

Changes in Beta weights when the mediator is present are highlighted in red.

Worry

IU

QoL

I

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B = .296*** B = -.729***

B = .546***

B = -.156** B = .067

B = -.364** B = .022

Figure 2. Mediation model showing that the effect of intolerance of uncertainty and worry

(independent variables) on quality of life (outcome) is mediated by irritability (mediator).

Changes in Beta weights when the mediator is present are highlighted in red.

Irritability

IU

QoL

W

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B = -.156*

B = -.368

B = -.729**

ns

ns

ns

ns

Figure 3. Moderation model showing all significant main effects and insignificant interaction

effects on quality of life.

IU

W

I

IUxW

IUx

WxI

IUxWxI

QoL

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Highlights

Intolerance of uncertainty, worry and irritability have unique significant effects on quality

of life in persons with epilepsy.

Worry mediates the impact of Intolerance of uncertainty but not that of irritability.

Irritability mediates the impact of both intolerance of uncertainty and worry on quality of

life of PWE.

No significant moderation effects were noted.

Results underscore the important role of irritability in the quality of life of persons with

epilepsy