COGNITIVE DYSFUNCTION, DISSOCIATION AND QUALITY OF LIFE IN BIPOLAR AFFECTIVE DISORDERS IN REMISSION

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1 sychiatria Danubina, 2010; Vol. 22, No. 4, Medicinska naklada - Zagreb, Croatia Original aer COGNITIVE DYFUNCTION, DIOCIATION AND QUALITY OF LIFE IN BIOLAR AFFECTIVE DIORDER IN REMIION Klara Latalova 1,2, Jan rasko 1,2,3,4, Tomas Diveky 1,2, Dana Kamaradova 1,2 & Hana Velartova 1,2 1 Faculty of Medicine and Dentistry, University alacky Olomouc, Olomouc, Czech Reublic 2 Deartment of sychiatry, University Hosital Olomouc, Olomouc, Czech Reublic 3 rague sychiatric Centre, rague, Czech Reublic 4 Centre of Neurosychiatric tudies, rague, Czech Reublic received: ; revised: ; acceted: UMMARY Background: Biolar disorders are often associated with cognitive deficits, which have an influence on social functioning and the course of the illness. These deficits have an imact on occuational ability and social integration. ubjects and methods: To ascertain cognitive function, level of dissociation and quality of life and their interrelations in atients with biolar affective disorder in remission. Data from D2 Attention Test, Verbal Fluency Test and Trial Making Test, Dissociative Exeriences cale (DE). Quality of Life atisfaction and Enjoyment (Q-LE-Q) and M.I.N.I. (MINI-international neurosychiatric interview were statistically analyzed. Results: There are no significant correlations between alied cognitive tests and dissociation scale DE. There are no significant correlations between alied cognitive tests and dissociation scale DE. There were no differences between emloyed and unemloyed atients in DE, athological DE and in any of Q-.LE-Q domains. Conclusions: We need further research to exlore the role of cognitive functions and dissociation in biolar affective disorder and its relationshi to cognitive functions, emotional regulation, biological factors and theray outcome. Key words: biolar disorder - cognitive functions dissociation occuation - quality of life * * * * * INTRODUCTION The clinical resentation of biolar affective disorders often has an eisodic course, with individuals switching from distinct affective eisodes of deression, mania or hyomania, and euthymia. Although mood disturbances are the sine qua non of biolar disorder, contemorary research has ointed increasingly to nonaffective elements of sychoathology associated with this diagnosis. roblems with work and social functioning ersist for lengthy eriods in many atients with biolar disorder after the resolution of manic or deressive eisodes, even in the absence of subsyndromal affective symtoms (Basso et al. 2002, Thomson et al. 2005). These roblems oint to other factors that likely mediate functional recovery, including the ability to lan and think clearly, understand connection between everyday life situations and emotions, solve roblems with understanding of the context of the situation, use emotions as a tool for understanding interersonal situations, remember imortant information and others which can be roblematic if the erson dissociates. Cognitive imairment in biolar disorder A cross-sectional study comared 4 grous: manic or hyomanic biolars, deressed biolars, euthymic biolars, and healthy controls using a neurosychological test battery (Martinez-Aran et al. 2004). Each of the three biolar grous showed significant imairments in verbal memory and executive functions in comarison with controls. The most recent metaanalysis available used 45 studies comaring 1423 euthymic biolar atients with 1524 healthy controls (Bora et al. 2009). The results showed grou differences with medium to large effect sizes for measures of executive function, verbal memory, sychomotor seed, and sustained attention. Cognitive deficits have an influence on social functioning and the course of the illness. The rincial conclusion of these studies comaring various disease states within biolar disorder is that the cognitive imairment in euthymia is not substantially different from that in the manic or deressive state (Latalova et al. 2010a). These deficits have an imact on occuational ability and social integration. A recent review has identified 13 studies addressing the relationshi between cognitive imairments and functional outcomes in euthymic biolar atients in comarison with healthy controls (Wingo et al. 2009). ignificant relationshis between cognitive imairments and functional outcomes were reorted in 12 of the 13 studies reviewed. Dissociation in biolar disorder Dissociation as a clinical sychiatric condition has been defined rimarily in terms of the fragmentation and slitting of the mind and ercetion of the self and the body. Its clinical manifestations include altered 528

2 Klara Latalova, Jan rasko, Tomas Diveky, Dana Kamaradova & Hana Velartova: COGNITIVE DYFUNCTION, DIOCIATION AND QUALITY OF LIFE IN BIOLAR AFFECTIVE DIORDER IN REMIION sychiatria Danubina, 2010; Vol. 22, No. 4, ercetions and behavior, including derealization, deersonalization, and distortions of ercetion of time, sace, and body. everal studies confirmed the close association between deressive symtoms and dissociation (Lisanen et al. 2004, Maaranen et al. 2005). A high level of dissociation is tyical also for atients with borderline ersonality disorders (astucha et al. 2009; Zanarini et al. 2000). Our results suggest that the level of sychological dissociation in biolar atients is higher than in healthy controls (Latalova et al. 2010b). If the disorder develoed earlier, the level of athological dissociation was higher. Quality of life in biolar disorder The effects of treatment using QoL as an indicator have been studied in the field of clinical sychiatry, including treatments and rehabilitation for biolar disorder and schizohrenia (Michalak et al. 2005; idlova et al. 2010). The Quality of Life Enjoyment and atisfaction scale (Q-LE-Q) (Endicott et al. 1993) for subjective assessment of QoL, has been used in biolar atients in various clinical and research contexts (Ozer et al. 2002, erlis et al. 2004, Revicki et al. 2003, Ritsner et al. 2005). The quality of life in biolar atients has been comared with atients with schizohrenia, showing that there are higher mean scores in most Q-LE-Q summary scales in atients with biolar disorder and this has also been shown in some summary scales in comarison with healthy controls in another study. The relationshi between level of dissociation, cognitive functions and quality of life is unknown. Goals and hyotheses The aim of our study was to examine the cognitive function, level of dissociation and quality of life and their interrelations in atients with biolar affective disorder in remission. We hyothesized that higher levels of cognitive dysfunction is related to a higher level of dissociation and lower quality of life in biolar atients in remission. The second hyothesis is that atient with a job have better cognitive functions, lower level of dissociation and higher of quality of life. UBJECT AND METHOD The subjects were outatients diagnosed with biolar disorder according to ICD-10 research diagnostic criteria (1996). Their written consent to articiate in the research was given. atients fulfilling all of the following criteria were enrolled in the study: (a) resence of life time biolar disorder, (b) now in clinical remission (CGI- one or two). Demograhic data, including age, sex, age of the onset of the disorder, duration of disorder, number of sychiatric hosital admissions, numbers of manic and deressive eisodes, were obtained from the interview. The diagnosis of lifetime biolar disorder was confirmed according to the atients documentation and clinical interview. At the time of evaluation all the atients were in clinical remission as confirmed by an exerienced sychiatrist (Clinical Global Imression everity; CGI- one or two). Diagnosis was confirm with M.I.N.I. (MINIinternational neurosychiatric interview; heehan et al, 1998) evaluated by an exerienced sychiatrist. Doses of drugs were converted to defined daily doses using data rovided by the Czech tate Institute for Drug Control (2010). Assessment Cognitive functions were examined using D2 Attention Test, Verbal Fluency Test and Trial Making Test. The D2 test is a self-administered and time limited examination of selective attention. It measures quickness of elaboration, quality of effort and keeing the rules. The aim of the test is to find out d-letters with two lines in a time interval of 8 minutes. A standard test has 14 rows, every row with 47 marks. The marks used in the test are d and letters with one to four vertical lines, laced alone or in airs above or below the letter. The tested erson has 20 seconds for every row. The score of overall achievement reresents the sum of all rocessed items minus the overall sum of all the errors (Balcar 2000). The Verbal Fluency Test is very useful in diagnosis of organic diseases. The atient is instructed to say as many words as he knows, if the first letter will be N, then K and then. The words should not be names of laces, states, towns, countries and first names (also surnames). The time for every letter is 1 minute. The administrator should count how many words the atient has said for every letter. The raw score reresents the whole summation of all the words said by the atient (reiss et al. 2002). The Trial Making Test is a self administered test used in diagnosis of organic diseases and to examine the atients sychomotor temo, selective attention, concentration and flexibility. It consists of two arts, art A and art B. The instruction in art A is to connect numbers from 1 to 4 in the examle form and from 1 to 25 in the administration form. In art B the atient is instructed to connect numbers and letter from the alhabet, e.g. 1 A 2 B etc. The administrator should note the time the atient needs for art A and art B. The raw score reresents the whole time the atient needs to administer the test (reiss et al. 1995). sychological dissociative symtoms were examined using the Dissociative Exeriences cale (DE) (Carlson et al. 1991, Carlson & utman 1993). The DE is a self-administered 28-item inventory of sychological dissociation, where articiants are asked 529

3 Klara Latalova, Jan rasko, Tomas Diveky, Dana Kamaradova & Hana Velartova: COGNITIVE DYFUNCTION, DIOCIATION AND QUALITY OF LIFE IN BIOLAR AFFECTIVE DIORDER IN REMIION sychiatria Danubina, 2010; Vol. 22, No. 4, to indicate on a visual analog scale how often they exerience the dissociative symtoms (in ercentage of time). The Czech version of the scale is comarable to the original version in terms of its test-retest reliability, validity and factor structure (tacek et al. 2007). athological DE was measured by a Dissociative Exeriences cale Taxon (DE-T) (Waller et al. 1996). Based on the items of DE number 3, 5, 7, 8, 12, 13, 22 and 27. These items measure identity alteration, deersonalization, derealization, discontinuation of awareness, dissociative amnesia, and auditory hallucinations. Quality of Life atisfaction and Enjoyment (Q-LE- Q) is 93 questions divided into 8 domains answered mainly as a five-oint Likert - tye scale. It is mostly self-comleted, ossibly with the hel of investigator (Ritsner et al. 2005). Q-LE-Q is useful for assessment of life satisfaction and enjoyment in atients with schizohrenia, schizoaffective and mood disorder atients (Endicott et al. 1993). It takes from 20 to 40 minutes, according to the health status of the atient. The domains hysical health, feelings, leisure, social relations and overview of the quality of life are comleted by atients and the domains, work, home and school only where relevant (Müllerova et al. 2001). Ethical issues: The investigation was carried out in accordance with the latest version of the Declaration of Helsinki and ICH-GC guidelines (The International Conference on Harmonization, Good Clinical ractice, 1999). All articiants signed an informed consent before entering the study. Data analysis: The atient's demograhic and baseline clinical characteristics were analyzed using column statistics. Normal distribution of the demograhic and clinical variables was determined by the hairo-wilk W test. Differences between emloyed and unemloyed atients were analyzed using unair t-tests for indeendent grous and the Mann- Whitney test. For the analysis of categorical data we used the chi 2 test or Fisher s exact test. The relationshis between variables with normal distribution were calculated using earson correlation analysis, while earman correlation was used for variables with non-normal distribution of DE. The level of significance was set at <0.05. All analyses were conducted using TATITICA 9.0 software. REULT Twenty three atients (11 males and 12 females) with biolar affective disorder in clinical remission between 23 and 70 years of age (mean age 46.17±14.11) from the Outatient deartment of sychiatry Clinic of University Hosital Olomouc were recruited for this study. All atients had been hositalized for biolar disorder at some time in their ast history. All used sychotroic medication, mood stabilizers (n=21; mean defined daily dosage of mood stabilizers were 0.91±0.45); antisychotics (n=17; mean defined daily dosage of antisychotics were 1.01±0.56); antideressants (n=10; mean defined daily dosage of antideressant was 1.3±0.54); and some of them also benzodiazeines (n=8; mean defined daily dosage of benzodiazeines was 0.91±0.53). Doses of drugs were converted to defined daily doses using data rovided by the Czech tate Institute for Drug Control (ÚKL, 2010). Demograhic and clinical variables, mean scores of rating scales, DE and cognitive test scores see in table 1. Table 1. Mean demograhic and clinical variables, DE and cognitive test scores Age 46.17±14.11 ex Male Female Education Basic econdary school without graduation econdary school with graduation University Marital status ingle Married Unmarried living with artner Divorced Widower Emloyment status Yes No Modd stabilizers DDD (n=21) 0.91±0.45 Antisychotics DDD (n=17) 1.01±0.56 Antideressants DDD (n=10) 1.3±0.54 Benzodiazeines DDD (n=8) 0.91±0.53 Age of the disorder onset 32.78±8.09 Length of the disorder 13.52±9.15 Number of manias 2.61±2.15 Number of deressions 2.65±1.82 Number of hositalizations 2.65±2.85 Length of the clinical remission (years) 1.48±2.57 Number of suicidal attemts (n=10) 1.30±0.48 DE 13.27±9.23 athological DE 1.71±2.82 TMT-A 47.00±17.88 TMT-B ±69.32 D ±92.53 Verbal fluency 34.09±10.86 DDD = Daily Defined Dose; DE=Dissociative Exerience cale; TMT-A=Trial Making Test A; TMT-B=Trial Making Test B; D2=D2 Test 530

4 Klara Latalova, Jan rasko, Tomas Diveky, Dana Kamaradova & Hana Velartova: COGNITIVE DYFUNCTION, DIOCIATION AND QUALITY OF LIFE IN BIOLAR AFFECTIVE DIORDER IN REMIION sychiatria Danubina, 2010; Vol. 22, No. 4, Cognitive tests and DE correlations with clinical variables Main results of earson s and earman s correlations are resented in Table 2. There were no statistically significant correlations between cognitive and clinical variables. ositive association were found between number of manic eisodes and DE (ear man s r=0.42; <0.05) and between mean dosage of mood stabilizers and DE (earson s r=0.4462, <0.05). The comarisons of cognitive tests in emloyed and unemloyed biolar atients show statistically significant difference between these subgrous only in the D2 test (410.00±84.19 versus ±83.96; t=2.334; df=20; <0.05) (Figure 1). Table 2. earson s and earman s correlation coefficients between cognitive tests, DE, athological DE and main clinical variables Variables Age of the Duration Number of Number of Mean dosage of thymoge of anti- Mean dosa- Age of Number Number of disorder of the hositalizations attemts stabilisers sychotics suicidal the atient of manias deression onset disorder TMT-A TMT-B D Verbal fluency DE * * = earson s r; = earman s; r; *< emloyed unemloyed < ns ns ns 0 TMT A TMT B D2 verbal fluency Cognitive tests TMT-A= Trial Making Test A; TMT-B= Trial Making Test B; D2= D2 Test Figure 1. Comarison of cognitive tests in emloyed and unemloyed biolar atients in remission Quality of life domains correlations with clinical variables The correlation matrix of the scores for each of Q- LE-Q domains and clinical variables showed that the number of manic eisodes has ositive correlation with domain feelings (earman s r=0.55; <0.01), number of hositalizations with domain work (earman s r=0.65; <0.05) and number of hositalizations with domain leisure time (earman s r=0.42; <0.05). The correlation matrix of the scores of Q-LE-Q did not show correlation of any of the domains with the age, illness onset, illness duration and number of deression eisodes, and any of the clinical data with domains hysical health, household, social activities and general. (see Table 3). The results of QoL comarisons according the emloyment status are resented in table 5. The comarisons of Q-LE-Q domains in emloyed and unemloyed biolar atients show a statistically significant difference between these subgrous only in the Q-LE-Q sum (323.30±30.72 versus ±35.23; t=5.063, df=21; <0.0001) (see Table 4). 531

5 Klara Latalova, Jan rasko, Tomas Diveky, Dana Kamaradova & Hana Velartova: COGNITIVE DYFUNCTION, DIOCIATION AND QUALITY OF LIFE IN BIOLAR AFFECTIVE DIORDER IN REMIION sychiatria Danubina, 2010; Vol. 22, No. 4, Table 3. Mean scores of Q-LE-Q domains and correlations with sociodemograhic and clinical data Mean D Correlations Age hysical health ± Feelings ± Work (n=10) ± Household ± chool/study(n=0) Leisure ± ocial activities ± General ± Q-LE-Q sum ± = earson s r; = earman s; r; *<0.05; **<0.01 Illness onset Illness duration Number of manias ** Number of deressions Number of hositalizations * * Table 4. Comarison of the quality of life according emloyment status tatus omatic Feelings Work Household chool Leisure ocial General Q-LE-Q sum Emloyed Mean n=10 D ±30.72 Unemloyed Mean n=13 D ±35.23 tatistics: unair t-test ns ns - ns - ns ns ns < Q-LE-Q = Quality of Life atisfaction and Enjoyment Cognitive function, dissociation and quality of life Most of Q-LE-Q domains (hysical health, Feelings, Work, Household, Leisure, ocial activities) did not show any correlation with any of the cognitive tests, but domain General highly correlated with 3 of the cognitive tests (negatively with TMT-B: earson s r=-0.54, <0.01, ositively with D2 test: earson s r=0.54, <0.01 and negatively with Verbal fluency test: earson s r=-0.42, <0.05). There were not any correlations between DE or athological DE scores and scores of cognitive tests. athological DE is only negatively correlated with the ocial activity domain of Q-LE-Q (earson s r=-0.58, <0.01) (see Table 5). Table 5. Q-LE-Q domains correlations with cognitive tests DE TMT-A TMT-B D2 Verbal fluency DE athde hysical health Feelings Work (n=10) Household chool/study(n=0) Leisure ocial activities ** General ** 0.54 ** * Q-LE-Q sum * DE athde = earson s r; * = <0.05; ** = <0.01; athde= athological dissociation 532

6 Klara Latalova, Jan rasko, Tomas Diveky, Dana Kamaradova & Hana Velartova: COGNITIVE DYFUNCTION, DIOCIATION AND QUALITY OF LIFE IN BIOLAR AFFECTIVE DIORDER IN REMIION sychiatria Danubina, 2010; Vol. 22, No. 4, DICUION The study confirmed our hyotheses only artially. We hyothesized that higher level of cognitive dysfunction is related to a higher level of dissociation and lower quality of life in biolar atients in remission, but this is not true in our atients. There are not any significant correlations between alied cognitive tests and dissociation scale DE. It seems that dissociation is not art of cognitive imairment, but it is an indeendent (robably active) rocess. Also there are not any significant correlations between DE and Q- LE-Q domains. There was only one significant correlation between athological DE and Q-LE-Q domain ocial activities. This finding can indirectly strengthen revious considerations. Dissociation is the rocess which frequently grows u from interersonal traumatic exerience and could increase the roblems in social adatation, which could be seen in atients with high social roblems and high levels of dissociation, like borderline ersonality disorder (astucha et al. 2009). Our findings could indirectly confirm this seculation: atients with higher levels of dissociation reorted lower level of quality of life in the domain ocial activities. We found highly significant correlations between Q- LE-Q domain General and three of four alied cognitive tests (TMT-B, D2 test and Verbal fluency test), and between sum Q-LE-Q and Verbal fluency test. How to interret these findings is difficult. Domain General of Q-LE-Q contains general items of feelings well and these feelings could be ensured by cognitive functions like attention, memory and verbal ability. The second hyothesis was that emloyed atients will have better cognitive functions, lower level of dissociation and higher of quality of life. This could be true in the D2 test. Emloyed biolar atients significantly differ from unemloyed in this cognitive task, but not in other cognitive tests. There were no differences between emloyed and unemloyed atients in DE, athological DE and in any of Q-.LE-Q domains. Our study has substantial limitations that should be considered. To assess the level of dissociation, we used selfreort questionnaires. Future research should corroborate these questionnaires with clinician-rated instruments. Also the subjective self-rating measurements of QoL were used with unknown reliability in this oulation. QoL in our study was measured with the Quality of Life Enjoyment and atisfaction (Q-LE-Q) which is not a QoL questionnaire secific to biolar disorder. A further limitation of our study is in relatively small samle size of the atients, which made imossible the evaluation of different subgrous. atients were medicated and ossible side-effects could influence the cognitive functioning and dissociation. The cognitive effects of the medications used in biolar disorder may well go in either direction, even with the same drug. Meta-regressions indicated that medication was associated with imaired sychomotor seed and sustained attention (Bora et al. 2009): tudies that reorted a higher roortion of atients an antisychotics reorted lower sychomotor seed and more omission errors, antideressants were associated with lower sychomotor seed and more imaired erformance on Trail Making Test A. These associations between medications and test erformance of course do not necessarily imly that medications had any direct causative effect on the erformance. In our study the dosage of mood stabilizers ositively correlated with DE but not with cognitive tests. CONCLUION We need further research to exlore the role of cognitive functions and dissociation in biolar affective disorder and its relation to the cognitive functions, emotional regulation, biological factors and theray outcome. Research into cognitive imairments in biolar disorder has yielded results that lead to revisions of the clinical aroach to the illness. REFERENCE 1. Balcar K. Test of concentration D2. Testcentrum, rague, Basso MR, Lowery N, Neel J: Neurosychological imairment among manic, deressed, and mixed-eisode inatients with biolar disorder. Neurosychology 2002; 16: Bora E, Yucel M, antelis C: Cognitive endohenotyes of biolar disorder: a meta-analysis of neurosychological deficits in euthymic atients and their first-degree relatives. J Affect Disord 2009; 113(1-2): Carlson EB, utnam FW: An udate on the Dissociative Exerience cale: An udate on the Dissociative. 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