Journal of Affective Disorders 151 (2013) 378–383

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Journal of Affective Disorders

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Preliminary communication

Life events in bipolar patients: A comparative study with siblingsand healthy controls

Yousri El Kissi n, Mohamed W. Krir, Selma Ben Nasr, Raja Hamadou, Raja El Hedda,Souhail Bannour, Bechir Ben Hadj AliDepartment of Psychiatry, Farhat Hached Hospital, Ibn Jazzar Street, Sousse 4000, Tunisia

a r t i c l e i n f o

Article history:Received 26 March 2013Received in revised form9 May 2013Accepted 31 May 2013Available online 4 July 2013

Keywords:Life eventsBipolar disorderComparative studySiblingsHealthy controls

27/$ - see front matter & 2013 Elsevier B.V. Ax.doi.org/10.1016/j.jad.2013.05.098

esponding author. Tel.: +216 73219508, +2166 73223702.ail address: yousri.elkissi@rns.tn (Y. El Kissi).

a b s t a r c t

Background: While many studies have focused on life events in depressive disorders, data regardingthem in bipolar disorder are scant. The aim of this work was to explore the characteristics of life events inbipolar patients.Methods: Sixty bipolar patients have been included in our study. The evaluation focused on thesociodemographic and clinical characteristics with a standardized measurement of life events usingPaykel's interview. The results were compared with those of siblings and healthy controls groups.The three groups were matched for age and sex.Results: Compared to the controls, bipolar patients and their siblings had a higher global score of life eventsand more events in the fields of work, socio-family events and health. Bipolar patients reported more desirableevents compared with their siblings and controls. The siblings reported higher scores of uncontrollable andundesirable events than patients and controls, and a higher score of controllable events than patients.Limitations: The Paykel's interview has no validated Tunisian version, which could be a methodological bias inthe assessment of life events. Moreover, the assessment of the life events was made during the euthymic phaseof the bipolar disorder; however, there was no standardized measure of mood symptoms, to confirm thiseuthymia.Conclusion: Our findings could help in the identification of the etiopathogeny of bipolar disorder and wouldcontribute to improve the understanding and management of these patients focusing on the psychosocialaspect which is often overlooked.

& 2013 Elsevier B.V. All rights reserved.

1. Introduction

While many studies have focused on life events in depressivedisorders (Fountoulakis et al., 2006; Reyes-Rodriguez et al., 2013;Stegenga et al., 2012; Tao et al., 2011), data regarding them inbipolar disorder are scant. This shortage could be partly explainedby the fact that bipolar disorder has been considered for long ashaving a pure biological mechanism (Craddock and Sklar, 2009;Newberg et al., 2008).

More recent studies have suggested a multifactorial etiology forbipolar disorder, involving both biological and psychosocial factors(Brietzke et al., 2012; Pitchot et al., 2012). Indeed, besides individualvulnerability, environmental factors seem to contribute to the emer-gence of the disease as well as to its subsequent evolution (Urosevicet al., 2008).

Some studies that have examined stressful events in bipolardisorder found a significant increase in these events in the monthspreceding a depressive or manic relapse (Malkoff-Schwartz et al.,

ll rights reserved.

98468626;

1998, 2000). Family studies have also emerged trying to explorethe relationship between genetic factors and life events. Thesestudies have found that family members of bipolar patientsreported more life events than healthy controls but focused onlyon the progeny of bipolar patients (DelBello and Geller, 2001; Pettiet al., 2004). It is however known that mood symptoms duringchildhood and adolescence raise problems of differential diagnosiswith other disorders and their assessment in these age rangesrequires the use of specific tools (DelBello and Geller, 2001).

The aim of this work was to explore the characteristics of lifeevents in bipolar patients with a case-control study.

2. Methods

This is a descriptive and comparative study of case-control type.

2.1. Study population

2.1.1. The bipolar patients groupThe group of bipolar patients was recruited in the outpatient

psychiatry department in Farhat Hached hospital in Sousse from

Y.E. Kissi et al. / Journal of Affective Disorders 151 (2013) 378–383 379

patients with a type I or type II bipolar disorder according to thecriteria of the diagnostic and statistical manual of mental dis-orders, 4th edition, text revision (DSM-IV-TR) (AmericanPsychiatric Association, 2000).

Inclusion criteria were age ≥18 years, disorder lasting alreadyfor at least one year, remission from the last mood episode formore than four weeks and free consent of the patient to partici-pate in this study. Exclusion criteria were the lack of a sister or abrother having an age greater than or equal to 18 years and thelack of consent for convening a sibling.

According to these criteria, 60 patients were included.

2.1.2. The controls groupControls were recruited from the stomatology outpatient unit

at the same hospital. After consent, only healthy subjects withoutany personal or family history of mood or psychotic disorder wereincluded. The controls were age and sex matched with the bipolarpatients.

2.1.3. The siblings groupFor each included patient, one of his brothers or sisters was

invited to participate in the study. A motivational and reminderletter was sent to those who did not initially participate. As far aspossible, the invited brother or sister was of the same sex and theclosest in age in order to get the siblings group matched for sexand age with the patients group.

2.2. Data collection

2.2.1. Sociodemographic and clinical characteristicsData was collected using a designed questionnaire for bipolar

patients. A second questionnaire was used for sibling and controlsincluding sociodemographic characteristics, family and personalhistory.

–

Sociodemographic characteristics: age, sex, educational level,employment status, marital status and origin.

–

Table 1Sociodemographic characteristics of bipolar patients, siblings and controls.

Parameters Bipolar patients Siblings Controls p-value

Age 43710 41712 44710 NSSexe ratio 0.33 0.5 0.42 NSEducational level

Illiterate 11.70% 6.66% 6.66% NSPrimary school 43.30% 45.00% 30.00%Secondary school 33.30% 33.33% 46.66%University 11.70% 15.00% 16.66%

Employment statusUnemployed 53.33% 41.66% 51.66% NSIrregular employment 18.33% 8.33% 6.66%Regular employment 28.33% 50.00% 41.66%

Marital statusSingle 26.66% 18.33% 10.00% NSMarried 65.00% 68.33% 78.33%Divorced or widowed 16.66% 13.33% 11.66%

OriginUrban 50.00% 50.00% 63.30% o10−3

Semi-urban 31.70% 31.70% 0Rural 18.30% 18.30% 36.70%

Clinical characteristics: orphanage or parental separation dur-ing childhood (before age of 12 years), sexual or physical abuseduring childhood (before age of 12 years), substance use,criminal history, personal medical and psychiatric history,family history of psychiatric disorder, type of bipolar disorderand age of its onset, nature of mood episodes and treatment.

2.3. Standardized evaluation

- Screening for mood and psychotic disorders in the controls andsiblings groups was performed using the Mini International Neuro-psychiatric Interview Plus (MINI-Plus) (Sheehan et al., 1998): MINI-Plus is a diagnostic interview focused on the current and formermental illness. It explores most of disorders of the DSM-IV Axis I or the10th revision of the International Statistical Classification of Diseasesand Related Health Problems (ICD-10). It is also validated comparedwith the CIDI (Lecrubier et al., 1997) and with the SCID-P (Sheehanet al., 1997). This tool has been translated into Arabic tunisian dialect.The structured interview concerned the A, B, C, D and M modulesexploring present and past mood and psychotic disorders. Thisallowed the exclusion by an objective and standardized methodcontrols and siblings who had mood or psychotic disorders.

- Assessment of life events in the three groups was carried outusing Paykel's interview for recent life events (Paykel, 1997) which is asemi-structured interview, covering 64 well defined life events. Theseevents were divided into ten categories to facilitate the interpretationof results: work, education, finance, health, bereavement, relocation,romantic relationships and cohabitation, legality, socio-family events,

conjugal events. A translated version into Arabic Tunisian dialect wasused. Identifying life events concerned only the last six months. Foreach reported event, a detailed questioning was carried out todetermine its nature, beginning and all circumstances of appearance.The objective negative impact of the event was defined through itsexpected stressfulness taking into account its nature and circum-stances. Scores were attributed as follows: (1) severe negative impact;(2) pronounced negative impact; (3) moderate negative impact; (4)little negative impact and (5) no negative impact. A negative impactwas considered for 1, 2 and 3 scores.

Besides, the listed life events were grouped according to theirnature: desirable/undesirable (marriage/conflict, illness…) andcontrollable/uncontrollable (relocation/retirement…). It was Paykel,in 1971, who introduced the concepts of “desirability” and “control”of the event to allow a focused analysis of life events (Newman andBland, 1994).

2.4. Statistical analysis

Results were provided as descriptive statistics and were comparedusing χ2 tests for categorical variables and ANOVA tests for numericalvariables. The Fisher exact test was used for the low numbers. For allcomparisons, a threshold of 0.05 was assigned for significant associa-tions. For comparison of means, nil scores of life events wereeliminated when the standard deviations were higher than means.

3. Results

3.1. Sociodemographic characteristics: table 1

The mean age of bipolar patients was 43710.5 years and thisgroup was constituted predominantly of females with a sex-ratio of0.33. The three groups were matched for age and sex. In addition,there was no difference in their level of education, employment andmarital status. However, the control group was more frequently ofrural origin than the groups of patients and their siblings (po10−3).

3.2. Clinical characteristics

During their childhood, six patients reported orphanage, tworeported sexual or physical abuse and no one reported a parentalseparation. Addiction was observed in eleven patients to tobacco,

Y.E. Kissi et al. / Journal of Affective Disorders 151 (2013) 378–383380

in two patients to alcohol and in one patient to cannabis.No patient had a criminal history. Fourteen patients had at leastone suicide attempt, nine had a comorbid personality disorder(obsessive compulsive personality in five patients, histrionicpersonality in three patients and dependent personality in onepatient). Forty-three patients had a family history of psychiatricdisorder (bipolar disorder in 17 cases, depressive major disorder in17 cases and schizophrenia in nine cases). Forty-eight patients hada bipolar I disorder and twelve had a bipolar II disorder. The meanage at onset of the diseasse was 26.279 years. Data regardingmood episodes and treatment are presented in Table 2.

3.3. Life events: table 3

3.3.1. Global scoresFifty-three patients had at least one life event in the last six

months. The mean number of life events was 2.3871.77 and ofthose with an objective negative impact was 1.9271.07.The bipolar patients group and the siblings group had higher

Table 2Nature of the first mood episodes, number of mood episodes per year andtreatment in bipolar patients.

Nature of the first moodepisode

Number of mood episodesper year

Mood stabilizertreatement

Bipolar I disorderDepressive 20 Depressive 0.1370.16 None 1Manic 22 Manic 0.370.28 Lithim 12Mixed 6 Mixed 0.3770.75 Valproate 20

Hypomanic 0.4670.13 Carbamazepine 15Total 0.5270.31

Bipolar II disorderDepressive 11 Depressive 0.2870.19 None 6Hypomanic 1 Hypomanic 0.2170.15 Lithim 2

Total 0.3870.18 Valproate 4Carbamazepine 0

Table 3Distribution of life events scores among patients with bipolar disorder, their siblings an

Life events scores Bipolar patients Siblings

Global 2.3871.77 2.8272.22

Work 1.5070.97 1.4070.63

Health 1.1970.6 1.1970.40

Socio-family events 1.4470.78 1.4170.62

Controllable 1.2770.46 1.5570.78

Uncontrollable 1.3070.52 1.5670.67

Desirable 1.2270.44 1

Undesirable 2.0371.13 2.6371.33

P1: statistical signification between the group of patients and the group of controls, P2:P3: statistical signification between the group of patients and the group of siblings

global score of life events compared to the controls group. Therewere no significant differences between the bipolar patients andsiblings groups for the global score of life events. No significantdifference was found between the three groups on scores of eventshaving an objective negative impact.

3.3.2. Scores by fields of life eventsBipolar patients and their siblings reported more events than

controls in the fields of work, socio-family events and health.

3.3.3. Scores by nature of life eventsBipolar patients reported more desirable events compared with

their siblings and controls. The siblings reported a higher number ofuncontrollable and undesirable events than patients and controls,and a higher score of controllable events compared to patients.

4. Discussion

Although psychosocial factors seem to have a great impact onbipolar disorder (Alloy et al., 2005), the exact role of life events in itsetiopathogeny is still little studied. This role could be specifiedthrough comparative studies exploring particularities of life eventsin bipolar patients. To our knowledge, this would be the first studyassessing life events in bipolar patients in comparison to bothcontrols and siblings groups. The use of two comparison groupsaimed to identify specific characteristics of life events in bipolardisorder. Indeed, healthy individuals undergo stressful events with-out developing mental disorders. Similarly, only the comparison withsiblings can distinguish between what is inherent to the disease andwhat could correspond to the family environmental and geneticfactors.

Concerning the life events assessment tool, the choice of thePaykel's interview was motivated by its wide use in internationalstudies and its initial design for mood disorders (Urosevic et al.,2008). It allows identifying a wide range of events and measuring theobjective negative impact and the independence from the disease

d controls.

Controls Intergroup p-value Intragroup p-value

1.5471.44 Po10−3 P1¼0.042P2o10−3

P3 NS1 P¼0.009 P1¼0.007

P2o10−3

P3 NS1 P¼0.029 P1¼0.008

P2o10−3

P3 NS1.1770.38 P¼0.004 P1¼0.01

P2¼0.045P3 NS

1.3170.60 P¼0.007 P1 NSP2 NSP3¼0.027

1.2470.43 Po10−3 P1 NSP2o10−3

P3¼0.0021 Po10−3 P1¼0.019

P2 NSP3 o10−3

2.0070.98 P¼0.002 P1 NSP2¼0.019P3¼0.038

statistical signification between the group of siblings and the group of controls, and

Y.E. Kissi et al. / Journal of Affective Disorders 151 (2013) 378–383 381

(Mansour et al., 2005). In addition, studies focusing on the initialversion of this interview highlighted its sensibility and reliability indetecting life events (de Oliveira Md et al., 2003). Although thePaykel's interview allows the identification of events preceding theonset of the disease, evaluation in this study focused only on the lastsix months in order to limit the impact of forgetting. Indeed, the timeaffects remembering of life events and there would be an overalldecline in the number of events remembered over time (Amiel-Lebigre, 2004a). The nature of the event may also have a role, asundesirable events are forgotten faster than desirable events (Amiel-Lebigre, 2004b). In addition, it is often difficult to distinguish whetheran event preceded the episode or if it was its consequence (Alloyet al., 2005; Johnson, 2005).

4.1. Life events

Compared to the controls group, the bipolar patients reporteda higher number of life events. Other studies found similar results(Christensen et al., 2003; Rucklidge, 2006; Tillman et al., 2003).In order to explain the higher number of life events experienced bybipolar patients compared to healthy controls, several studies haveexamined the characteristics of patients and bipolar disorder: periodsof euthymia in bipolar disorder are typically considered to be free ofpsychiatric symptoms, however, it seems now established that manypatients have residual symptoms during this period. Indeed, it hasbeen found that 24% of bipolar patients kept mood symptoms duringthe intervals between mood episodes (Angst, 1980) and bipolarpatients in remission had higher scores on scales of depression andmania (Kaya et al., 2007). It has also been described that residualsymptoms interested cognitive-behavioral, mood and social spheres,which may be responsible for an impaired functioning betweenepisodes and therefore generate life events (Keitner et al., 1996). Thisfinding can also be explained by the temperaments described inbipolar patients. Indeed, several studies have described personalitytraits or specific temperaments in patients with bipolar disorder andmost of studies have reported that euthymic bipolar patients hadhigher impulsivity scores compared to healthy controls (Peluso et al.,2007; Swann et al., 2001; Swann et al., 2003). This would imply thatimpulsivity is stable and independent of mood episodes (Keitneret al., 1996). Some authors have even postulated the existence ofa common pathophysiology between bipolar disorder and impulsiv-ity (Swann et al., 2004). Impulsivity has been linked to risk-taking,sensation seeking, lack of planning and quick decision-making(Moeller et al., 2001), which would be the cause of the increase inlife events. It has also been found that bipolar patients had higherrates of cyclothymia, extraversion, novelty search and hostility (Savitzet al., 2008). All these traits could create circumstances facilitating theoccurrence of life events (Alloy et al., 2005).

Compared with the controls group, siblings of bipolar patientshad also reported a higher number of life events. Some studiessimilarly found a higher number of life events in descendants ofbipolar patients (Petti et al., 2004; Wals et al., 2005). The explanationfor this might correspond to individual endophenotypes(Mendlowicz et al., 2005). In addition, a higher prevalence ofcyclothymic temperament in healthy members of bipolar patientsfamilies than in controls was found (Mendlowicz et al., 2005), whichcould be the cause of the higher number of life events (Lovejoy andSteuerwald, 1995). A literature review exploring the personalityprofiles of adolescents and young adults from bipolar parents, foundthat they had high scores on Zuckerman's scale of sensation seekingand especially on the subscale of disinhibition (Jones and Bentall,2008) which could favor the occurrence of life events.

No differences were found in the occurrence of life events withan objective negative impact between the three groups. Only onestudy found a similar result (Havermans et al., 2007), however,several studies found that bipolar patients, during and outside

mood episodes, had inadequate responses to stressful events,which increases their negative impact (Alloy et al., 2005;Rucklidge, 2006). This difference could be explained by the factthat investigation of life events concerned those with an objectivenegative impact, whereas most of studies focused on the sub-jective impact experienced by patients.

4.2. Fields of life events

Bipolar patients had higher scores in the field of work comparedto the controls group. Indeed, bipolar disorder is a chronic diseasethat affects the professional functioning with higher rates of absen-teeism and cognitive deterioration which could be responsible for adecrease of work capacity (Fajutrao et al., 2009).

Consistently with other studies (Hammen and Brennan, 2002;Kim et al., 2007; Newman and Bland, 1994), socio-family events weremore frequent in bipolar patients than in controls. This can beexplained by stable and generalized interpersonal difficulties inseveral areas even outside mood episodes and these difficulties wereattributed to dysfunction in relational skills and cognitive representa-tions of interpersonal relationships (Hammen and Brennan, 2002).

Significant somatic and psychiatric comorbidity could explainthe high scores in the field of health among bipolar patientscompared to controls (Friedlander et al., 2002).

Siblings group reported also higher scores in the fields of work,health and socio-family events compared to controls. High scoresin socio-family events could be part of the interpersonal difficul-ties that siblings could live in relation to personality traits of thefamily members of bipolar patients. Indeed it has been found thatdescendants of bipolar patients reported more stressful events withinthe context of interpersonal relationships (Ostiguy et al., 2009).

4.3. Nature of life events

Bipolar patients reported more desirable events compared to theirsiblings and to controls. To our knowledge, this result has not beenfound by other studies. This could be explained by the fact that mostof studies have focused on assessing the nature of life eventspreceding the episodes of the disease. Patients in this study havebeen assessed in the euthymic phase and could then have experi-enced a higher number of desirable events which would have beenfavored by specific traits such as extraversion (Savitz et al., 2008).

Siblings reported a higher number of uncontrollable eventsthan patients and controls. Through a literature review, it has beenfound that teenagers and young children of bipolar parentsreported more uncontrollable events compared to healthy controls(Jones and Bentall, 2008). This was explained by the fact that theseyoung people were exposed to stressful events related to aconflictual and unstable family environment, characterized bylow family cohesion generated by bipolar parents.

4.4. Limitations

The Paykel's interview has no validated Tunisian version, whichcould be a methodological bias in the assessment of life events.The assessment did not concern life events prior to mood episodesand was made during the euthymic phase of the bipolar disorder;however, there was no standardized measure of mood symptomsto confirm this euthymia.

Despite the pioneering nature of this study, it would beinteresting to evaluate bipolar patients during intervals by usingother standardized measures of personality traits, impulsivity andtemperaments. This assessment, moreover if it is prospective,would provide more details on the modalities of interactionbetween genetic and environmental factors in bipolar disorder.

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5. Conclusion

The existence of a relationship between life events andpsychiatric disorders is now well established. However, fewstudies have investigated the role of life events in bipolar disorder.This study describes, with a standardized and comparativemethod, the characteristics of life events among patients withbipolar disorder. Compared to controls, bipolar patients had higherglobal score of life events, more events in the fields of work, socio-family events and health and more desirable events. These find-ings could help in the identification of the etiopathogeny ofbipolar disorder and would contribute to improve the under-standing and management of these patients focusing on thepsychosocial aspect which is often overlooked.

Role of funding sourceNo funding source was provided for this study.

Conflict of interestNone of the authors has any conflict of interests to declare.

AcknowledgmentsThe authors thank Doctor Ghanem Amara and Doctor Neila Ben Salah who

assisted with the proof-reading of the manuscript.

References

Alloy, L.B., Abramson, L.Y., Urosevic, S., Walshaw, P.D., Nusslock, R., Neeren, A.M.,2005. The psychosocial context of bipolar disorder: environmental, cognitive,and developmental risk factors. Clinical Psychology Review 25, 1043–1075.

Amiel-Lebigre, F., 2004a. Événements stressants de la vie: méthodologie etrésultats. EMC—Psychiatrie 1, 75–86.

Amiel-Lebigre, F., 2004b. Psychosocial factors associated to depressive episodeswith hospitalization in women: a case-control study. L’Encephale 30, 97–105.

Angst, J., 1980. Course of unipolar depressive, bipolar manic-depressive, and schizoaf-fective disorders. Results of a prospective longitudinal study (author's transl).Fortschritte der Neurologie, Psychiatrie, und ihrer Grenzgebiete 48, 3–30.

American Psychiatric Association, 2000. Diagnostic and Statistical Manual ofMental Disorders DSM-IV-TR, fourth ed. American Psychiatric Association,Washington, DC. (Text revision).

Brietzke, E., Mansur, R.B., Soczynska, J.K., Kapczinski, F., Bressan, R.A., McIntyre, R.S.,2012. Towards a multifactorial approach for prediction of bipolar disorder in atrisk populations. Journal of Affective Disorders 140, 82–91.

Christensen, E.M., Gjerris, A., Larsen, J.K., Bendtsen, B.B., Larsen, B.H., Rolff, H., Ring, G.,Schaumburg, E., 2003. Life events and onset of a new phase in bipolar affectivedisorder. Bipolar Disorders 5, 356–361.

Craddock, N., Sklar, P., 2009. Genetics of bipolar disorder: successful start to a longjourney. Trends in Genetics: TIG 25, 99–105.

de Oliveira Md, M., Fonseca, P.P., del Porto, J.A., 2003. Inter-rater reliability of theBrazilian version of the Paykel scale of stressful life events. Psychopathology 36,320–323.

DelBello, M.P., Geller, B., 2001. Review of studies of child and adolescent offspring ofbipolar parents. Bipolar Disorders 3, 325–334.

Fajutrao, L., Locklear, J., Priaulx, J., Heyes, A., 2009. A systematic review of theevidence of the burden of bipolar disorder in Europe. Clinical Practice AndEpidemiology in Mental Health: CP & EMH 5, 3.

Fountoulakis, K.N., Iacovides, A., Kaprinis, S., Kaprinis, G., 2006. Life events andclinical subtypes of major depression: a cross-sectional study. PsychiatryResearch 143, 235–244.

Friedlander, A.H., Friedlander, I.K., Marder, S.R., 2002. Bipolar I disorder: psycho-pathology, medical management and dental implications. Journal of theAmerican Dental Association 133, 1209–1217.

Hammen, C., Brennan, P.A., 2002. Interpersonal dysfunction in depressed women:impairments independent of depressive symptoms. Journal of AffectiveDisorders 72, 145–156.

Havermans, R., Nicolson, N.A., Devries, M.W., 2007. Daily hassles, uplifts, and timeuse in individuals with bipolar disorder in remission. Journal of Nervous andMental Disease 195, 745–751.

Johnson, S.L., 2005. Life events in bipolar disorder: towards more specific models.Clinical Psychology Review 25, 1008–1027.

Jones, S.H., Bentall, R.P., 2008. A review of potential cognitive and environmental riskmarkers in children of bipolar parents. Clinical Psychology Review 28, 1083–1095.

Kaya, E., Aydemir, O., Selcuki, D., 2007. Residual symptoms in bipolar disorder: theeffect of the last episode after remission. Progress in Neuro-Psychopharmacology &Biological Psychiatry 31, 1387–1392.

Keitner, G.I., Solomon, D.A., Ryan, C.E., Miller, I.W., Mallinger, A., Kupfer, D.J., Frank, E.,1996. Prodromal and residual symptoms in bipolar I disorder. ComprehensivePsychiatry 37, 362–367.

Kim, E.Y., Miklowitz, D.J., Biuckians, A., Mullen, K., 2007. Life stress and the courseof early-onset bipolar disorder. Journal of Affective Disorders 99, 37–44.

Lecrubier, Y., Sheehan, D.V., Weiller, E., Amorim, P., Bonora, I., Harnett Sheehan, K.,Janavs, J., Dunbar, G.C., 1997. The Mini International Neuropsychiatric Interview(MINI). A short diagnostic structured interview: reliability and validity accordingto the CIDI. European Psychiatry 12, 224–231.

Lovejoy, M.C., Steuerwald, B.L., 1995. Subsyndromal unipolar and bipolar disorders:comparisons on positive and negative affect. Journal of Abnormal Psychology104, 381–384.

Malkoff-Schwartz, S., Frank, E., Anderson, B., Sherrill, J.T., Siegel, L., Patterson, D.,Kupfer, D.J., 1998. Stressful life events and social rhythm disruption in the onsetof manic and depressive bipolar episodes: a preliminary investigation. Archivesof General Psychiatry 55, 702–707.

Malkoff-Schwartz, S., Frank, E., Anderson, B.P., Hlastala, S.A., Luther, J.F., Sherrill, J.T.,Houck, P.R., Kupfer, D.J., 2000w. Social rhythm disruption and stressful lifeevents in the onset of bipolar and unipolar episodes. Psychological Medicine 30,1005–1016.

Mansour, H.A., Talkowski, M.E., Wood, J., Pless, L., Bamne, M., Chowdari, K.V., Allen, M.,Bowden, C.L., Calabrese, J., El-Mallakh, R.S., Fagiolini, A., Faraone, S.V., Fossey, M.D.,Friedman, E.S., Gyulai, L., Hauser, P., Ketter, T.A., Loftis, J.M., Marangell, L.B.,Miklowitz, D.J., Nierenberg, A.A., Patel, J., Sachs, G.S., Sklar, P., Smoller, J.W., Thase,M.E., Frank, E., Kupfer, D.J., Nimgaonkar, V.L., 2005. Serotonin gene polymorph-isms and bipolar I disorder: focus on the serotonin transporter. Annals ofMedicine 37, 590–602.

Mendlowicz, M.V., Jean-Louis, G., Kelsoe, J.R., Akiskal, H.S., 2005. A comparisonof recovered bipolar patients, healthy relatives of bipolar probands, and normalcontrols using the short TEMPS-A. Journal of Affective Disorders 85,147–151.

Moeller, F.G., Barratt, E.S., Dougherty, D.M., Schmitz, J.M., Swann, A.C., 2001. Psychiatricaspects of impulsivity. American Journal of Psychiatry 158, 1783–1793.

Newberg, A.R., Catapano, L.A., Zarate, C.A., Manji, H.K., 2008. Neurobiology ofbipolar disorder. Expert Review of Neurotherapeutics 8, 93–110.

Newman, S.C., Bland, R.C., 1994. Life events and the 1-year prevalence of majordepressive episode, generalized anxiety disorder, and panic disorder in acommunity sample. Comprehensive Psychiatry 35, 76–82.

Ostiguy, C.S., Ellenbogen, M.A., Linnen, A.M., Walker, E.F., Hammen, C., Hodgins, S.,2009. Chronic stress and stressful life events in the offspring of parents withbipolar disorder. Journal of Affective Disorders 114, 74–84.

Paykel, E.S., 1997. The interview for recent life events. Psychological Medicine 27,301–310.

Peluso, M.A., Hatch, J.P., Glahn, D.C., Monkul, E.S., Sanches, M., Najt, P., Bowden, C.L.,Barratt, E.S., Soares, J.C., 2007. Trait impulsivity in patients with mooddisorders. Journal of Affective Disorders 100, 227–231.

Petti, T., Reich, W., Todd, R.D., Joshi, P., Galvin, M., Reich, T., Raymond DePaulo, J.,Nurnberger, J., 2004. Psychosocial variables in children and teens of extendedfamilies identified through bipolar affective disorder probands. BipolarDisorders 6, 106–114.

Pitchot, W., Scantamburlo, G., Ansseau, M., Souery, D., 2012. Bipolar disorder: amultifactorial disease. Revue Medicale De Liege 67, 366–373.

Reyes-Rodriguez, M.L., Rivera-Medina, C.L., Camara-Fuentes, L., Suarez-Torres, A.,Bernal, G., 2013. Depression symptoms and stressful life events among collegestudents in Puerto Rico. Journal of Affective Disorders 145, 324–330.

Rucklidge, J.J., 2006. Psychosocial functioning of adolescents with and withoutpaediatric bipolar disorder. Journal of Affective Disorders 91, 181–188.

Savitz, J., van der Merwe, L., Ramesar, R., 2008. Hypomanic, cyclothymic and hostilepersonality traits in bipolar spectrum illness: a family-based study. Journal ofPsychiatric Research 42, 920–929.

Sheehan, D.V., Lecrubier, Y., Harnett Sheehan, K., Janavs, J., Weiller, E., Keskiner, A.,Schinka, J., Knapp, E., Sheehan, M.F., Dunbar, G.C., 1997. The validity of the MiniInternational Neuropsychiatric Interview (MINI) according to the SCID-P and itsreliability. European Psychiatry 12, 232–241.

Sheehan, D.V., Lecrubier, Y., Sheehan, K.H., Amorim, P., Janavs, J., Weiller, E.,Hergueta, T., Baker, R., Dunbar, G.C., 1998. The Mini-International Neuropsy-chiatric Interview (M.I.N.I.): the development and validation of a structureddiagnostic psychiatric interview for DSM-IV and ICD-10. Journal of ClinicalPsychiatry 59 (Suppl. 20), 22–33. (quiz 34-57).

Stegenga, B.T., Nazareth, I., Grobbee, D.E., Torres-Gonzalez, F., Svab, I., Maaroos, H.I.,Xavier, M., Saldivia, S., Bottomley, C., King, M., Geerlings, M.I., 2012. Recent lifeevents pose greatest risk for onset of major depressive disorder during mid-life.Journal of Affective Disorders 136, 505–513.

Swann, A.C., Anderson, J.C., Dougherty, D.M., Moeller, F.G., 2001. Measurementof inter-episode impulsivity in bipolar disorder. Psychiatry Research 101,195–197.

Swann, A.C., Dougherty, D.M., Pazzaglia, P.J., Pham, M., Moeller, F.G., 2004.Impulsivity: a link between bipolar disorder and substance abuse. BipolarDisorders 6, 204–212.

Swann, A.C., Pazzaglia, P., Nicholls, A., Dougherty, D.M., Moeller, F.G., 2003. Impulsi-vity and phase of illness in bipolar disorder. Journal of Affective Disorders 73,105–111.

Tao, M., Li, Y., Xie, D., Wang, Z., Qiu, J., Wu, W., Sun, J., Wang, Z., Tao, D., Zhao, H., Tian, T.,Zhang, J., Gao, C., Niu, Q., Li, Q., Liu, S., Liu, J., Zhang, Y., He, Q., Rong, H., Gan, Z., Li, J.,Chen, X., Pan, J., Li, Y., Cui, Y., Han, W., Ma, H., Xie, S., Jin, G., Li, L., Zhang, R., Tan, Q.,Zhang, J., Guan, J., Shi, S., Chen, Y., Kendler, K.S., Flint, J., Gao, J., 2011. Examining the

Y.E. Kissi et al. / Journal of Affective Disorders 151 (2013) 378–383 383

relationship between lifetime stressful life events and the onset of majordepression in Chinese women. Journal of Affective Disorders 135, 95–99.

Tillman, R., Geller, B., Nickelsburg, M.J., Bolhofner, K., Craney, J.L., DelBello, M.P.,Wigh, W., 2003. Life events in a prepubertal and early adolescent bipolardisorder phenotype compared to attention-deficit hyperactive and normalcontrols. Journal of Child and Adolescent Psychopharmacology 13, 243–251.

Urosevic, S., Abramson, L.Y., Harmon-Jones, E., Alloy, L.B., 2008. Dysregulation of thebehavioral approach system (BAS) in bipolar spectrum disorders: review oftheory and evidence. Clinical Psychology Review 28, 1188–1205.

Wals, M., Hillegers, M.H., Reichart, C.G., Verhulst, F.C., Nolen, W.A., Ormel, J., 2005.Stressful life events and onset of mood disorders in children of bipolar parentsduring 14-month follow-up. Journal of Affective Disorders 87, 253–263.