Psychiatry Research 196 (2012) 145–153

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Psychiatry Research

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Psychosocial and neurocognitive functioning in unipolar and bipolar depression: A12-month prospective study

Julie Godard a,b,d,⁎, Philippe Baruch a, Simon Grondin b,c, Martin F. Lafleur a

a Institut universitaire en santé mentale de Québec, Québec, Canadab École de psychologie, université Laval, Québec, Canadac Centre interdisciplinaire de recherche en réadaptation et intégration sociale, Québec, Canadad Centre de réadaptation en déficience physique Le Bouclier, Joliette, Canada

⁎ Corresponding author at: École de Psychologie, UBibliothèques, Sainte-Foy, Québec, Canada, G1V 0A6. Te418 656 3646.

E-mail address: julie_godard@hotmail.com (J. Godar

0165-1781/$ – see front matter. Crown Copyright © 20doi:10.1016/j.psychres.2011.09.013

a b s t r a c t

a r t i c l e i n f o

Article history:Received 21 January 2011Received in revised form 9 July 2011Accepted 17 September 2011Available online 3 February 2012

Keywords:NeuropsychologyCognitionPsychosocial functioningMajor depressive disorderBipolar disorder

Previous studies have revealed psychosocial and cognitive impairments in patients during unipolar and bipo-lar depression, which persist even in subsyndromal and euthymic states. Currently, little is known about thenature and the extent of psychosocial and cognitive deficits during depression. The aim of the present studywas to characterize psychosocial and cognitive profiles among unipolar (MDD) and bipolar (BD) patientsduring a major depressive episode and to compare the profiles of the patient groups. Depressed patientswith MDD (n=13) and BD (n=11) were followed over a period of 12 months. Clinical, psychosocial andneuropsychological assessments were conducted at baseline and at 6-week, 4-month, 8-month and12-month follow-ups. In the case of severe mood disorders, psychosocial and neurocognitive functioningseem similar among MDD and BD patients during a depressive episode. All MDD and BD patients had globalpsychosocial dysfunction, characterized by occupational and relational impairments. Furthermore, the neuro-cognitive profile was heterogeneous with regard to the nature and extent of cognitive deficits but attentionalprocesses were frequently compromised. After 1 year of treatment, occupational and relational impairments,as well as neurocognitive dysfunction, persisted sufficiently to alter daily functioning.

Crown Copyright © 2012 Published by Elsevier Ireland Ltd. All rights reserved.

1. Introduction

Mood disorders are highly prevalent and constitute a major publichealth problem. After an affective episode, most patients with majordepressive disorder (MDD) and bipolar disorder (BD) reach partialor complete remission (Spijker et al., 2002). However, residual symp-toms persist frequently beyond an affective episode (Paykel et al.,2006; Kupka et al., 2007). During the euthymic phase, MDD and BDpatients spend considerable time with depressive symptoms atminor or subsyndromal level (Judd et al., 1998, 2002). In addition tochronicity, the long-term course of illness is characterized by recurrence.Within 5 years of a major depressive episode, 70% of MDD (Holma et al.,2008) and 88% of BD (Keller, 2004a) patients have at least one relapse.Over a lifetime, patients have more than five major depressive episodes(Kessler and Walters, 1998). Compared to MDD patients, those withBD have shorter and less severe depressive episodes (Mansell et al.,2005) and fewer residual symptoms (Vieta et al., 2008).

Depression has an important impact on psychosocial functioning.According to the World Health Organization (WHO, 2004), MDD

niversité Laval, 2325 rue desl.: +1 418 656 2131; fax: +1

d).

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and BD rank as two of the 10 leading causes of disability. During adepressive episode, MDD and BD are often associated with wide-spread impairments in all domains of functioning. Impaired perfor-mance relative to household and work, days missed from work, andwork disability are commonly observed during unipolar and bipolardepression (Adler et al., 2006; Simon et al., 2008). The quality ofrelationships with partners, family members (Weinstock et al.,2006; Marangell et al., 2009) and friends (Altshuler et al., 2006) isalso compromised, along with the frequency of social and leisureactivities (Ruggero et al., 2007). These occupational, social and rela-tional dysfunctions reduce the quality of life of depressed patientswith MDD (Strine et al., 2009) and BD (Gutiérrez-Rojas et al., 2008).Psychosocial functioning appears to be strongly associated withdepressive symptoms (Adler et al., 2006; Rytsälä et al., 2006; Berlimet al., 2007; Simon et al., 2007; Reed et al., 2009). Although improve-ment of symptomatology is related to fewer occupational and relationaldeficits, patients with minor or subsyndromal levels of depression havepsychosocial impairments similar to thosewithmajor depression. Somedegree of impairment remains present evenduring remission (Kennedyet al., 2007;Marangell et al., 2009). A 15-year follow-up amongunipolarand bipolar patients showedmoderate to severe dysfunctionmore than26% of the time (Judd et al., 2008), indicating the impact of depressionon daily functioning. Almost all psychosocial impairments seem to becomparable among unipolar and bipolar patients during the course of

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Table 1Demographic and clinical characteristics of patients with major depressive disorder(MDD) and bipolar disorder (BD) (values are expressed as mean or frequency, standarddeviation is shown in parentheses).

MDD group(n=13)

BD group(n=11)

Tests

χ2 or t

Demographic characteristicsAge 49.3 (12.0) 45.5 (10.2) t=0.82Education (years) 14.6 (3.1) 14.6 (3.6) t=−0.15

Characteristics of the illnessAge at onset 35.2 (12.0) 32.4 (10.6) t=0.61Duration of illness (years) 13.8 (12.7) 13.5 (9.7) t=0.08Duration of actual episode (months) 24.1 (22.4) 8.1 (17.3) t=1.93Number of episodesDepressive episodes 2.2 (1.5) 2.9 (1.5) t=−1.11Total episodes 2.5 (1.8) 5.2 (2.4) t=

−3.16⁎⁎

Suicide attempts 0.8 (1.0) 0.5 (1.0) t=0.73Hospitalizations 2.8 (2.8) 3.2 (3.0) t=−0.29Psychotic symptomsActual (number of patients) 1 2 χ2=0.60Past (number of patients) 1 3 χ2=1.65

Medications, n (%)Antidepressants 13 10 χ2=1.23Mood stabilizers 7 10 χ2=3.96Benzodiazepines 12 6 χ2=4.53Hypnotics/sedatives 1 0 χ2=0.88Neuroleptics 7 6 χ2=0.00

Co-morbid disordersAnxiety disorders 2 2 χ2=0.03Eating disorders 1 0 χ2=0.88ADHD 0 1 χ2=1.23Somatoform disorders 1 0 χ2=0.88Substance disorders 1 6 χ2=6.33⁎

Personality disorders 4 5 χ2=0.51

⁎ pb0.05.⁎⁎ pb0.01.

146 J. Godard et al. / Psychiatry Research 196 (2012) 145–153

the illness (Ruggero et al., 2007). Compared to MDD, however, BD isassociated with more work disability (Ruggero et al., 2007; Judd et al.,2008).

Cognitive deficits seem to explain certain occupational andpsychosocial impairments (Jaeger et al., 2006; Wingo et al., 2009).Unipolar and bipolar depressions are frequently associated with dys-function across a range of neurocognitive domains, including attention,executive functions, as well as learning and memory (Marvel andParadisø, 2004; Haldane and Frangou, 2006). Patterns of cognitiveimpairments are similar in unipolar and bipolar depression (Quraishiand Frangou, 2002; Marvel and Paradisø, 2004) but deficits are moresevere in BD (Murphy and Sahakian, 2001; Mansell et al., 2005).

A number of studies have demonstrated cognitive deficits inattention with regard to alertness (McIntosh et al., 2005; Pardo etal., 2006), information processing speed (Tsourtos et al., 2002;Burdick et al., 2009), vigilance and sustained attention (Porter et al.,2003; Depp et al., 2007), as well as selective (Politis et al., 2004;Burdick et al., 2009) and divided (Lemelin and Baruch, 1998) attention.In addition to learning andmemory impairments (Martínez-Arán et al.,2004; Bearden et al., 2006), executive dysfunction has also beenreported with respect to inhibition (Gohier et al., 2009; Swann et al.,2009), working memory (Christopher and MacDonald, 2005; Glahn etal., 2006) and cognitive flexibility (Martínez-Arán et al., 2004; Depp etal., 2007; Gohier et al., 2009). However, other studies have revealedgood performance onmeasures of attention (Pardo et al., 2006), execu-tive functions (Rund et al., 2006), learning and memory (Wang et al.,2006). Although improvement of symptomatology is related to greaterneurocognitive functioning, patients with subsyndromal depressionpresent subtle cognitive deficits. Even in remission, such deficits persist,suggesting the possibility of trait markers (Robinson et al., 2006; Smithet al., 2006; Torres et al., 2007; Bora et al., 2009).

While it is commonly accepted that psychosocial and cognitive im-pairments are associated with MDD and BD, attempts to specify profilesand evolution in unipolar and bipolar depression have not been conclu-sive. Currently, little is known about the nature and extent of the psycho-social and cognitive deficits observed in depressed patients with MDDand BD. The disparity in findings may be explained by differences acrossstudies with regard to the selection of participants. Indeed, age range,severity and length of illness, as well as medications, may influence psy-chosocial and neurocognitive functioning. Moreover, variability in studydesign and methodology also contributes to the inconsistency of results.

The aim of the present study was to characterize the psychosocialand neurocognitive profiles of MDD and BD patients during majordepressive episodes through a 12-month follow-up. We thereforeexamined the nature and extent of impairments and compared theprofiles of the patient groups. With regard to psychosocial functioning,we hypothesized that depressed patientswith BDwould have relationaland social impairments similar to those with MDD, but poorer occupa-tional functioning. It was also predicted that the two patient groupswould have similar neurocognitive profiles, involving some deficits onmeasures of attention, executive functions, learning and memory.Heterogeneity in neurocognitive functioning was also anticipated. Wehypothesized that psychosocial and neurocognitive functioning wouldimprove progressively as depressive severity decreased.

2. Methods

2.1. Subjects

Thirty patientswere included in the study. Theywere recruited at themood disordersclinic of the Institut universitaire en santémentale de Québec. Six patients dropped out ofthe study and 24 completed the follow-ups. Based on theMini International Neuropsychi-atric Interview (MINI; Sheehan et al., 2002), 13 patients met the criteria for a Diagnosticand Statistical Manual of Mental Disorders (DSM-IV-TR) diagnosis of major depressivedisorder (MDD: one man, 12 women), seven the criteria for a DSM-IV-TR diagnosis of bi-polar I disorder (BDI: fourmen, three women) and four the criteria for a DSM-IV-TR diag-nosis of bipolar II disorder (BDII: two men, two women). All patients were recruitedduring a depressive episode, and none had a manic episode throughout the 12-month

follow-up. At the time of their initial assessment, they began a newpharmacological treat-ment. The medications are described in Table 1. As for additional treatments, 11 patients(eight MDD, three BD) received psychotherapy and three patients (one MDD, two BD)electroconvulsive therapy (ECT). Some patients had co-morbid psychiatric disorders,which are detailed in Table 1. Exclusion criteria were: co-morbid psychotic disorder, his-tory of moderate or severe head injury, neurological disorder, mental retardation, historyof learning disabilities, and age outside the range of 18–65 years. The control group con-sisted of 30 subjects who did not have an actual depressive episode or a history of psychi-atric illness. The patients and healthy controls were matched by age and years ofeducation. Healthy controls completed only CogitEx II tasks.

2.2. Clinical assessment

In addition to MINI, all patients were evaluated with the Hamilton DepressionRating Scale (HDRS-17; Hamilton, 1960), the Montgomery Asberg Depression RatingScale (MADRS; Montgomery and Asberg, 1979) and the Young Mania Rating Scale(YMRS; Young et al., 1978). Furthermore, patients completed the Beck DepressionInventory (BDI-II; Beck et al., 1996) and the Beck Anxiety Inventory (BAI; Beck andSteer, 1990). Information was also collected about medical and psychiatric illness.

2.3. Psychosocial assessment

Psychosocial functioning was assessed with the Longitudinal Interval Follow-upEvaluation-Range of Impaired Functioning Tool (LIFE-RIFT; Leon et al., 1999). Thisscale assessed overall psychosocial functioning and comprised the Work, Interpersonalrelationships, Life satisfaction, and Recreation subscales. These subscales were addedtogether to obtain a single score ranging from 4 (no impairment, high functioning) to20 (severe impairment). For the Work and Relationships subscales, the ratings for theworst work and relationship categories were employed in the LIFE-RIFT calculation.

2.4. Neuropsychological assessment

Patients completed an extensive neuropsychological battery to assess attention,executive functions, verbal learning and memory, as well as visual functions. Thesetests are briefly summarized below, as detailed descriptions are available elsewhere.

2.4.1. AttentionContinuous Performance Test (CPT-II; Conners, 2000), Delis-Kaplan Executive

Function System (D-KEFS: Color Word Interference Test; Delis et al., 2001) and CogitEx

147J. Godard et al. / Psychiatry Research 196 (2012) 145–153

II (Simple Reaction Time Test, Divided Attention Test, Conditional Reaction Time Test,Choice Reaction Time Test: Laplante and Baruch, 1999). CogitEx II is a battery of com-puterized cognitive tasks. The Simple Reaction Time Test consists in pressing a buttonas quickly as possible when a circle on a screen turns white. The Divided Attention Testinvolves the same task, in addition to simultaneous counting aloud. The ConditionalReaction Time Test requires subjects to rapidly press a button when a circle on a screenturns green and to refrain from pressing the button when the circle turns red. In theChoice Reaction Time Test, three circles are presented on a screen and one of theseturns white. Subjects must quickly press the button corresponding to the target.

2.4.2. Executive functionsD-KEFS (Color–Word Interference Test, Verbal Fluency Test, Design Fluency Test,

Tower Test, Twenty Questions Test: Delis et al., 2001) and CogitEx II (SequentialMemorisation Test: Laplante and Baruch, 1999). In the Sequential Memorisation Test,arrows (↑,↓) are presented one by one. The task consists in identifying the directionof the next-to-last arrow.

2.4.3. Verbal learning and memoryCalifornia Verbal Learning Test (CVLT-II; Delis et al., 2000) was used to test verbal

learning and memory.

2.4.4. Visual functionsBlock Design (Wechsler Abbreviated Scale of Intelligence: WASI; Chen et al., 1999)

was used to assess visual functions.

2.4.5. Intellectual abilitiesVocabulary and Matrix (WASI; Chen et al., 1999) were used to test intellectual abilities.

2.5. Procedure

Patients were enrolled during a major depressive episode. Assessments were con-ducted at baseline and at 6-week, 4-month, 8-month and 12-month follow-ups. Thesame clinical, psychosocial and neuropsychological assessments were carried out atbaseline and at the 12-month follow-up, which required two, 2-hour sessions. At the6-week, 4-month and 8-month follow-ups, symptom severity and psychosocial func-tioning were also assessed and cognitive tasks with minimal practice effects wereadministered. These assessments took 2 h. Breaks were allowed to avoid fatigue. Thestudy was approved by the relevant ethical committees.

2.6. Statistical analysis

2.6.1. Demographic and clinical characteristicsMDD and BD groups were compared on demographic and clinical variables by

using independent sample t-tests and chi-squared, as appropriate.

2.6.2. SymptomatologySymptom severity was compared across time and the various groups by means of

repeated-measures analysis of variance (ANOVA) for each instrument. If the maineffect was significant, dependent sample t-tests were performed. The percentages oftreatment response and remission were also calculated at each follow-up. Treatmentresponse was defined as a 50% decrease in the scores on HDRS-17 and MADRS fromthe baseline scores (Keller, 2004b). Remission corresponded to a score≤7 on HDRS-17and a score≤10 on MADRS (Zimmerman et al., 2004).

2.6.3. Psychosocial functioningPsychosocial variables were compared across time and the MDD and BD groups by

means of multivariate analysis of variance (MANOVA). If the main effect was signifi-cant, repeated-measures ANOVA was performed for each psychosocial domain,followed by dependent sample t-tests. The proportion of patients with significantpsychosocial impairment was calculated. Patients were considered to have impairmentif their scores were at or above 3 by psychosocial domain and at or above 13 in all.

2.6.4. Neuropsychological functioningA MANCOVA was conducted using all neuropsychological measures and time

(baseline, 12-month follow-up) as dependent variables, patient groups (MDD andBD) as factors, and current IQ as covariate. A second set of MANCOVA using IntelligenceQuotient (IQ) as covariate was conducted on all neuropsychological measures adminis-tered at each follow-up (baseline, 6-week, 4-month, 8-month, 12-month) in order tocompare time and group effects. If themain effect of timewas significant, dependent sam-ple t-tests and repeated-measures ANCOVAs were performed, if applicable, for each cog-nitive variable. As many of the tests used in this study are naturally correlated, thisprocedure was considered superior to a Bonferroni inequality correction that wouldtend to increase type II error. These analyses excluded data from patients receiving ECT.

The raw scores of all neuropsychological tests were converted into Z-scores on thebasis of the standardized normative data or the data for the control group (CogitEx II).The Z-scores were then grouped by cognitive domain (attention, executive functions,verbal learning and memory, visual functions) and specific function. In order to assessthe proportion of patients with significant cognitive impairment, a cut-off score of 1S.D. below the mean of normative data or control group was used as a threshold.Patients were then considered to have cognitive impairment in a given function if at

least one variable of this function had a Z-score inferior to 1 S.D. below the mean.This criterion was established because some cognitive functions were assessed byonly one variable. Chi-square analyses were used to compare the percentage ofimpaired patients at baseline and the 12-month follow-up. Data analyses wereperformed using the SPSS 13.0 statistical package.

3. Results

3.1. Clinical assessment

The clinical and demographic features of the MDD and BD patientsare shown in Table 1. No difference was found between groups withrespect to age (t (22)=0.82, p=0.421) and years of education (t(22)=−0.15, p=0.988). With regard to co-morbid disorders, onlysubstance disorders were more frequent among bipolar patients (χ2

(1)=6.33, p=0.023). Moreover, MDD and BD patients did not differsignificantly with respect to age at onset (t (22)=0.61, p=0.545),duration of illness (t (22)=0.08, p=0.939) or actual episode (t(22)=1.93, p=0.066), number of hospitalizations (t (22)=−0.29,p=0.778) and suicide attempts (t (22)=0.73, p=0.475). Whereasthe number of previous depressive episodes was comparable betweengroups (t (22)=−1.11, p=0.280), bipolar patients had more affectiveepisodes (t (22)=−3.16, p=0.004).

3.2. Assessment of symptomatology

The scores obtained with clinical tools assessing symptomatologyare shown in Table 2. The MANOVA did not reveal significant differ-ences between MDD and BD groups in the HDRS (F (1, 22)=1.27,p=0.273), MADRS (F (1, 22)=0.44, p=0.514), BDI-II (F (1, 22)=0.59, p=0.054), YMRS (F (1, 22)=4.16, p=0.054), and BAI (F (1,22)=1.01, p=0.327) scores. At baseline, patients manifested moder-ate to severe depression and moderate anxiety. Follow-up was charac-terized by improvement in depressive symptoms (HDRS: F (4, 19)=9.16, pb0.001; MADRS: F (4, 19)=8.70, pb0.001; BDI-II: F (4, 19)=6.47, p=0.002) but not in anxiety (BAI: F (4, 19)=2.22, p=0.105). Infact, the severity of depressive symptoms was significantly improvedas early as 6 weeks following the start of treatment. About 20% ofpatients presented treatment response after 6 weeks and about 50%after 8 months. By the 12-month follow-up, only one-third of patientshad achieved complete remission.

3.3. Psychosocial assessment

The results of the psychosocial assessments conducted throughoutthe follow-up are presented in Table 3. The MANOVA did not revealany significant differences in psychosocial functioning between theMDD and BD groups (F (1, 22)=0.08, p=0.775). At baseline, patientsmanifested mild to moderate deficits concerning interpersonal rela-tionships and recreational activities. They were moderately to severe-ly dysfunctional with regard to employment, housework, and lifesatisfaction. In sum, psychosocial functioning was globally altered atthe beginning of depression. Follow-up was characterized by psycho-social improvement (F (4, 19)=8.50, pb0.001). Patients presentedgreater functioning with respect to recreational activities and greaterlife satisfaction 6 weeks after treatment began. By the 8-monthfollow-up, functioning in employment and housework had improved;by the 12-month follow-up, relationships with relatives had alsoimproved. However, other types of relationships remained stableover time. Fig. 1 illustrates the percentage of impaired patients bypsychosocial domain throughout the follow-up. At baseline, all butone patient was dysfunctional in all domains. After 1 year of treatment,about 75% of patients still presented employment and relational func-tioning deficits. Housework, recreational activities and life satisfactionalso remained dysfunctional for about 50% of patients.

Table 2Scores of clinical tools obtained by patients as a function of the follow-up condition (values are expressed as mean, standard deviation is shown in parentheses).

Baseline(T1)

6-week(T2)

4-month(T3)

8-month(T4)

12-month(T5)

ANOVAsd.f. (4, 19)

t-tests

HDRS-17 19.0 (5.0) 13.3 (6.8) 13.1 (6.9) 9.5 (8.5) 10.1 (6.4) F=9.155⁎⁎⁎ T1>T2, T3, T4, T5T2>T4

MADRS 26.5 (7.3) 17.7 (8.8) 17.0 (9.7) 15.1 (11.6) 13.3 (9.4) F=8.699⁎⁎⁎ T1>T2, T3, T4, T5BDI-II 34.5 (11.7) 25.9 (14.3) 28.0 (15.7) 22.6 (17.4) 21.8 (16.3) F=6.465⁎⁎ T1>T2, T4, T5YMRS 1.5 (2.8) 1.2 (1.3) 1.3 (2.0) 0.8 (1.2) 1.2 (1.6) F=0.737BAI 22.0 (13.9) 17.0 (10.7) 16.4 (13.5) 17.5 (14.7) 14.5 (12.9) F=2.222

⁎⁎ pb0.01.⁎⁎⁎ pb0.001.

148 J. Godard et al. / Psychiatry Research 196 (2012) 145–153

3.4. Neuropsychological assessment

Table 4 shows performance on the cognitive tasks with minimalpractice effects administered at each follow-up. The MANCOVArevealed significant differences over time (F (4, 15)=7.02, p=0.002)but no significant difference between the groups (F (1, 18)=0.002,p=0.961). Inhibition (CogitEx II–RT conditional test/commissions: F(4, 15)=5.07, p=0.009) improved during the follow-up (T1bT4: t(20)=−3.27, p=0.004; T3bT4: t (20)=−2.47, p=0.023).

The results of the neuropsychological assessments made at bothbaseline and 12-month follow-up are presented in Table 5. The MAN-COVA revealed significant differences over time (F (1, 17)=15.97,p=0.001) and no significant difference between the groups (F (1,17)=0.06, p=0.815). In comparison to baseline, the cognitiveperformance obtained at the 12-month follow-up was significantlybetter with regard to information processing speed (CogitEx II–RTconditional test/RT: t (20)=−2.24, p=0.036), sustained attention(CPT-II/omissions: t (20)=−2.70, p=0.014), spontaneous flexibility(Design Fluency/combined filled dots and empty dots: t (20)=−2.86, p=0.010), planning (Tower/total achievement: t (20)=−2.24, p=0.037), as well as encoding (CVLT-II/trials 1–5 total: t(20)=−2.42, p=0.037) and retrieval (CVLT-II/short delay freerecall: t (20)=−3.37, p=0.003; CVLT-II/short delay cued recall: t(20)=−2.72, p=0.013; CVLT-II/long delay free recall: t (20)=−2.80, p=0.011) in verbal memory.

The average percentage of patients scoring more than 1 S.D. belowthe mean of normative data on cognitive tasks at baseline and12-month follow-up is presented in Fig. 2. Attentional processes(alertness, information processing speed, sustained and dividedattention) were the most frequently impaired cognitive functions,as well as spontaneous flexibility. The most rarely impaired includedupdating in working memory, planning, abstraction, storage in verbal

Table 3Psychosocial functioning as a function of the follow-up condition (values are expressed as

Baseline(T1)

6-week(T2)

4-month(T3)

8-m(T4)

Occupational functioningEmployment 4.7 (0.7) 4.6 (1.0) 4.3 (1.2) 3.6Housework 4.3 (0.6) 3.7 (1.1) 3.3 (1.3) 3.0Recreation 3.9 (0.8) 3.0 (1.2) 2.8 (1.2) 2.9

Relational functioningSpouse 3.4 (0.9) 3.4 (1.0) 2.3 (1.6) 3.1Children 3.1 (1.4) 3.1 (1.3) 2.8 (1.6) 2.6Other relatives 3.6 (1.3) 3.2 (1.3) 3.2 (1.2) 3.0Friends 3.3 (1.4) 3.3 (1.2) 2.9 (1.2) 3.1

Life satisfaction 4.0 (0.8) 3.1 (1.1) 3.1 (1.1) 3.0Total 17.1 (2.1) 14.7 (3.2) 14.0 (3.8) 13.5

Psychosocial domains (Work, Relationships, Life satisfaction, Recreation) of LIFE-RIFT: 1=verTotal: sum of these domains ranging from 4 (no impairment, high functioning) to 20 (severe

⁎ pb0.05.⁎⁎ pb0.01.⁎⁎⁎ pb0.001.

memory and visual functions. Between the baseline and 12-monthfollow-up conditions, chi-square analyses revealed only a significantdifference in the proportion of patients with impairments in verballearning and memory deficit (χ2 (1)=6.86, p=0.020), namely inencoding task (χ2 (1)=6.04, p=0.032).

Despite improved performances in certain cognitive tasks, theneurocognitive profile of the MDD and BD patients remained relativelystable over time. Most patients (T1: 86%; T5: 71%) presented deficits inmore than one cognitive domain, whereas few manifested only atten-tional (T1: 5%; T5: 14%) or executive (T1: 10%; T5: 0%) impairmentsor had no cognitive deficit (T1: 0%; T5: 14%). At both baseline (T1)and 12-month follow-up (T5), the majority of patients showed atten-tional (T1: 90%; T5: 86%) and executive (T1: 95%; T5: 71%) dysfunctions.Some of them presented verbal learning andmemory deficits (T1: 52%;T5: 14%) and few had visual impairments (T1: 5%; T5: 10%).

4. Discussion

To our knowledge, this is one of rare prospective studies to charac-terize and to compare both psychosocial and neurocognitive profilesof MDD and BD patients during major depressive episodes througha 12-month follow-up. The clinical, psychosocial and neurocognitiveprofiles associated with unipolar and bipolar depression are discussedbelow.

4.1. Symptomatology

The MDD and BD patients enrolled in this study presented similardepressive and anxious severity throughout the follow-up. At base-line, patients manifested moderate to severe depression and moderateanxiety. Contrary to anxiety, depressive symptomatology improvedduring follow-up, as early as 6 weeks after the start of treatment.

mean, standard deviation is shown in parentheses).

onth 12-month(T5)

ANOVAs t-tests

(1.6) 4.0 (1.4) F=4.861⁎⁎ T1>T4; T2>T4(1.4) 2.8 (1.3) F=9.367⁎⁎⁎ T1>T4, T5(1.1) 2.3 (1.3) F=8.428⁎⁎⁎ T1>T2, T3, T4, T5

(1.1) 2.1 (1.2) F=1.211(1.4) 2.5 (1.4) F=1.360(1.4) 2.5 (1.5) F=2.814⁎ T1>T5(1.0) 2.9 (1.4) F=0.941(1.1) 2.7 (1.2) F=8.795⁎⁎⁎ T1>T2, T3, T4, T5(3.7) 12.4 (4.1) F=12.047⁎⁎⁎ T1>T2, T3, T4, T5; T2>T5

y good; 2=good; 3= fair; 4=poor; 5=very poor.impairment).

22 23 24 2423

18

17

16

20

14

19

18

14

20

16

11

17

121312

13

17

10

13

16

0

20

40

60

80

100

Employment Housework Leisure Relationships Life satisfactionFunctional domains

% im

pai

red

pat

ien

tsBaseline 6-week 4-month 8-month 12-month

Fig. 1. The percentage of impaired patients on psychosocial domains as a function ofthe follow-up condition. The numbers above each column represent the actual numberof patients for each period. Because data for certain patients were not included forcertain domains (e.g., patients who were retired were not included in the Employmentdomain), the total number of patients may differ from one domain to another.

149J. Godard et al. / Psychiatry Research 196 (2012) 145–153

However, by the 12-month follow-up, less than half of patients showedtreatment response andonly one-third had achieved complete remission.Rates of treatment response and remission were thus lower than thosereported in previous studies. Indeed, treatment response, which is de-fined by a decrease of at least 50% in initial symptoms, (Montgomery,1994; Keller, 2004b), generally appears 4 to 6 weeks following the startofmedication (Boulenger, 2004).Moreover, Spijker et al. (2002) reporteda remission rate of 76% amongMDD patients in 1 year. The present studysuggests that remission of depression takes longer in the context of asevere and complex mood disorder than in that of a mild and puredepressive episode.

This persistence of residual symptoms can be explained by certainfactors related to the history of depression among the patients in thisstudy. Depressive severity, longer duration of the illness and thecurrent episode, numerous affective episodes, and the presence ofpsychiatric comorbidity are considered factors that negatively influence

Table 4Neuropsychological performances in Z-Scores as a function of the follow-up condition (valu

Baseline(T1)

6-week(T2)

AttentionAlertnessCPT-II: hit RT 0.4 (1.5) 0.2 (1.5)CPT-II: hit RT SE −1.0 (1.6) −1.2 (1.8)CogitEx II: simple RT test (RT) −2.0 (3.0) −1.6 (2.5)

Information processing speedCogitEx II: choice RT test (RT) −2.6 (3.0) −2.4 (2.7)CogitEx II: conditional RT test (RT) −2.3 (2.7) −2.0 (2.6)

Sustained attentionCPT-II: omissions −1.3 (2.5) −0.4 (1.3)CPT-II: hit RT BC −0.5 (1.2) −0.3 (0.8)CPT-II: hit RT SE BC −0.5 (1.1) −0.7 (1.2)

Divided attentionCogitEx II: Divided Attention Test (RT) −1.7 (2.3) −2.1 (2.9)CogitEx II: Divided Attention Test (errors) −1.2 (2.1) −1.1 (1.3)

Executive functionsInhibitionCogitEx II: conditional RT test (commissions) −0.5 (1.3) 0.1 (1.1)C–W interference: inhibition vs color −0.1 (0.9) 0.2 (0.8)C–W interference: inhibition (errors) −0.3 (1.1) −0.4 (1.2)

Reactive flexibilityC–W interference: switching vs inhibition −0.2 (1.6) 0 (1.2)UpdatingCogitEx II: Sequential Memorisation Test 0 (0.9) −0.2 (0.9)

C–W interference: Color–Word Interference Test (D-KEFS).⁎⁎ pb0.01.

the course of the illness and predispose patients to chronicity of symp-toms (Spijker et al., 2004; Holma et al., 2008).

4.2. Psychosocial functioning

As expected, psychosocial functioning was globally impaired forall MDD and BD patients at baseline, with deficits altering functioningat occupational and relational levels. Moderate to severe impairmentsin patients' work and home functioning roles were observed, as wellas mild to moderate impairments in relationships. Patients not onlyneglected housework, but also performed poorly at work or pre-sented work disability. Their involvement in recreational activitieswas also limited and they derived little enjoyment from such activities.Their relations with their family members and friends were character-ized by conflicts or limited contacts. Consequently, patients were verydissatisfied in most areas and derived little pleasure from life. Previousresearch has also reported a loss of efficiency at work, absenteeism orwork disability (Adler et al., 2006; Altshuler et al., 2006; Gardner etal., 2006; Simon et al., 2008; Marangell et al., 2009), as well as interper-sonal difficulties (Judd et al., 2000; Altshuler et al., 2006; Marangell etal., 2009) and altered quality of life and well-being (Kuehner andBuerger, 2005; Gutiérrez-Rojas et al., 2008; Strine et al., 2009), duringa major depressive episode.

As hypothesized, psychosocial functioning progressively improvedduring follow-up as depressive severity decreased. Six weeks after thestart of medication, patients showed better life satisfaction and becamemore involved in leisure. This functional improvement also coincidedwith a significant decrease in depressive severity. With respect toemployment and housework functioning, patients showed betterperformances only at the 8-month follow-up. Although marital, paren-tal and friendly relations remained stable, patients had more frequentand harmonious relations with their other relatives by the end of thefollow-up. These results are consistentwith previous studies suggestinga progressive improvement of psychosocial functioning and quality oflife with the attenuation of depressive symptomatology (Adler et al.,2006; Rytsälä et al., 2006; Berlim et al., 2007; Simon et al., 2007; Reedet al., 2009). The present study has thus made it possible to describe

es are expressed as mean, standard deviation is shown in parentheses).

4-month(T3)

8-month(T4)

12-month(T5)

MANCOVAsd.f. (4,15)

t-tests

0.4 (1.1) 0.7 (1.2) 0.6 (1.4) F=2.312−0.8 (1.6) −0.6 (1.8) −0.6 (1.6) F=1.042−1.5 (2.2) −1.3 (1.8) −1.1 (1.4) F=1.024

−2.7 (2.9) −2.0 (2.1) −1.7 (2.1) F=1.068−2.2 (2.7) −1.6 (2.9) −1.5 (2.2) F=1.954

−0.9 (2.1) −0.6 (2.4) −0.4 (1.7) F=2.249−0.5 (0.9) −0.1 (1.1) −0.3 (1.2) F=0.690−0.8 (1.1) −0.5 (1.1) −0.7 (0.9) F=0.191

−1.8 (2.1) −1.5 (2.3) −1.6 (2.4) F=0.697−1.0 (2.2) −0.8 (2.0) −1.0 (1.9) F=0.273

−0.3 (1.6) 0.4 (1.1) −0.3 (1.1) F=5.071⁎⁎ T1bT4; T3bT4−0.1 (0.8) 0.1 (0.5) 0 (0.9) F=0.941−0.4 (1.3) −0.2 (1.1) −0.1 (1.0) F=0.780

0.5 (1.0) 0.3 (0.9) 0.1 (1.0) F=1.156

0.1 (1.1) 0 (0.9) 0.3 (1.1) F=0.794

Table 5Neuropsychological performances in Z-Scores at baseline and 12-month follow-up(values are expressed as mean, standard deviation is shown in parenthesis).

Baseline 12-month t-tests

AttentionAlertnessCPT-II: hit RT 0.4 (1.5) 0.6 (1.4) −0.87CPT-II: hit RT SE −1.0 (1.6) −0.6 (1.6) −1.95CogitEx II: simple RT test −2.0 (3.0) −1.1 (1.4) −1.75

Information processing speedCogitEx II: choice RT test −2.6 (3.0) −1.7 (2.1) −1.78CogitEx II: conditional RT test −2.3 (2.7) −1.5 (2.2) −2.24⁎

Sustained attentionCPT-II: omissions −1.3 (2.5) −0.4 (1.7) −2.70⁎

CPT-II: hit RT block change −0.5 (1.2) −0.3 (1.2) −0.51CPT-II: hit RT SE block change −0.5 (1.1) −0.7 (0.9) 0.68

Divided attentionCogitEx II: Divided Attention Test (RT) −1.7 (2.3) −1.6 (2.4) −0.34CogitEx II: Divided Attention Test

(errors)−1.2 (2.1) −1.0 (1.9) −0.43

Executive functionsInhibitionCogitEx II: conditional RT test

(commissions)−0.5 (1.3) −0.3 (1.1) −0.36

C–W interference: inhibition vs color −0.1 (0.9) 0 (0.9) −0.71C–W interference: inhibition (errors) −0.3 (1.1) −0.1 (1.0) −1.02

Reactive flexibilityC–W interference: inhibition/switching

vs inhibition−0.2 (1.6) 0.1 (1.0) −1.00

Design Fluency: switching vs(filled+empty)

0.3 (0.6) 0 (0.8) 1.49

Verbal Fluency: category switching vscategory

0.4 (0.7) 0.5 (1.1) −0.43

Spontaneous flexibilityVerbal Fluency: letter fluency −0.9 (0.9) −0.7 (0.7) −1.51Verbal Fluency: category fluency −1.1 (1.1) −0.8 (1.3) −0.75Design Fluency: combined filled

dots+empty dots−0.5 (0.9) 0 (1.0) −2.86⁎

UpdatingCogitEx II: Sequential Memorisation Test 0 (0.9) 0.3 (1.1) −1.18

PlanningTower: total achievement −0.5 (0.8) 0 (1.2) −2.24⁎

AbstractionTwenty Questions: initial abstraction −0.1 (0.8) 0 (0.8) −0.17Twenty Questions: total weighted

achievement0.4 (0.9) 0.1 (0.8) −0.46

Verbal learning and memoryEncodingCVLT-II: trials 1–5 total −0.6 (1.4) 0.1 (1.2) −2.42⁎

RetrievalCVLT-II: short delay free recall −0.8 (1.3) 0 (1.1) −3.37⁎⁎

CVLT-II: short delay cued recall −0.8 (1.4) 0.1 (1.3) −2.72⁎

CVLT-II: long delay free recall −0.8 (1.5) 0.1 (1.3) −2.80⁎

CVLT-II: long delay cued recall −0.6 (1.2) 0 (1.3) −2.08StorageCVLT-II: total recognition discriminality −0.2 (1.2) 0.2 (1.2) −1.38

Visual functionsAnalysis/synthesisWASI: block Design −0.3 (0.7) −0.2 (0.8) −0.63

⁎ pb0.05.⁎⁎ pb0.01.

1

5

99

12

17

1413

2

9

14

65

1 2 2 3 2

15

9 11

1

7

10

4 3

0

20

40

60

80

100

Alert

IPS

Sust.

att.

Div. a

tt.

Up da

ting

Inhib

ition

Spont

. fl.

React.

fl.

Plannin

g

Abstra

ction

Encod

ing

Retrie

val

Stora

ge

Visual

Cognitive functions

% im

pai

red

pat

ien

ts Baseline

12-month

Fig. 2. The percentage of impaired patients in each cognitive function at baseline and12-month follow-up. The numbers above each column represent the actual numberof patients for each period. Information processing speed (IPS), sustained attention(sust. att.), divided attention (div. att.), spontaneous flexibility (spont. fl.), reactiveflexibility (react fl.).

150 J. Godard et al. / Psychiatry Research 196 (2012) 145–153

short-term changes in daily functioning during a major depressiveepisode.

After 1 year of treatment, about 75% of patients still presented em-ployment and relational functioning deficits. Housework, recreationalactivities, and life satisfaction also remained dysfunctional for about50% of patients. Even though a mild improvement in functioningwas observed, occupational and relational difficulties persisted signif-icantly for most patients. Their daily functioning was substantiallyimpaired, along with their life quality. Other studies have also notedthe persistence of considerable psychosocial impairments in the sub-syndromal phase of depression (Kennedy et al., 2007; Marangell etal., 2009) and even in periods of remission (Kennedy et al., 2007;Gutiérrez-Rojas et al., 2008). The magnitude and frequency of

occupational, relational and social impairments at the end of thefollow-up could be explained by the presence of poorer prognosticfactors, namely, major depressive severity, longer illness, a chronicor recurrent course, and the presence of psychiatric comorbidity(Rytsälä et al., 2006; Kennedy et al., 2007).

As expected, depressed patients with BD had relational and socialimpairments similar to those with MDD. However, in contrast to ourhypothesis and the results of previous studies, BD patients did nothave poorer occupational functioning than MDD patients. This con-tradiction of previous research could be explained by the fact thatthe bipolar patients included in that research generally had moresevere illness than the unipolar patients. Indeed, the unipolar andbipolar patients involved in the present study had a similar severityof depression and history of illness. All patients were moderately toseverely depressed and had a chronic or recurrent evolution. It ispossible therefore that severity of depression and history of illnesscould have greater impact on occupational functioning than the diag-nosis itself.

4.3. Neurocognitive functioning

The neurocognitive profile observed in the MDD and BD patientswas similar and characterized by heterogeneity regarding the natureand extent of cognitive deficits. Some patients had adequate neuro-cognitive functioning, while most of themmanifested different cogni-tive deficits. This is consistent with the few studies carried out amongMDD (Rund et al., 2006) and BD patients (Martino et al., 2008;Simonsen et al., 2008) and suggests that the neurocognitive profilesassociated with mood disorders are heterogeneous, regardless of thephase of the illness.

At baseline, the majority of patients showed attentional and execu-tive dysfunctions. Some presented verbal learning andmemory deficits,while few had visual function impairments. Previous studies haverevealed attentional, executive and mnesic deficits during depression(Quraishi and Frangou, 2002; Marvel and Paradisø, 2004). In ourstudy, themost frequently impaired cognitive functions were alertness,information processing speed, sustained and divided attention, as wellas spontaneous flexibility. Whereas all attentional processes were im-paired, the nature of executive functions was more specific and variedamong patients. In addition to exhibiting slowed cognitive processes,patients were less able to mobilize their attentional resources andcarry out simultaneous tasks. They also had difficulty generating strate-gies or solutions in order to resolve problems.

Basic cognitive processeswere thus particularly affected and complexcognitive functions, such as abstraction and planning, seem relativelypreserved. These results are consistent with those of previous studies.Deficits have been reported with regard to alertness (McIntosh et al.,2005; Pardo et al., 2006), information processing speed (Tsourtos et al.,

151J. Godard et al. / Psychiatry Research 196 (2012) 145–153

2002; Burdick et al., 2009), sustained (Porter et al., 2003; Depp et al.,2007) and divided attention (Lemelin and Baruch, 1998).

Contrary to previous research, this study suggests that executivefunctions, as well as verbal learning and memory, were better pre-served than attentional processes during unipolar and bipolar depres-sion. It is possible that executive (Harvey et al., 2004; Summers et al.,2006; Depp et al., 2007) and mnesic (Martínez-Arán et al., 2004;Bearden et al., 2006) deficits observed in several studies reflect mainlyan impairment in attentional processes.

As hypothesized, better cognitive performance was progressivelyobtained in certain cognitive tasks as depressive severity decreased.After 1 year of treatment, patients presented improved performanceon measures of information processing speed, sustained attention,spontaneous flexibility, planning, as well as encoding and retrievalin verbal learning and memory. Despite these cognitive improvements,the neurocognitive profile was relatively similar at both baseline and12-month follow-up, characterized frequently by generalized atten-tional dysfunction and specific executive deficits. Moreover, the neuro-cognitive profile of bothMDD and BD patients was similar at the end ofthe follow-up, regardless of whether or not they were in remission.

These results support those of previous studies reporting smallercognitive impairments during subsyndromal depression, aswell as sub-tle neurocognitive dysfunction even during remission (Robinson et al.,2006; Smith et al., 2006; Torres et al., 2007; Bora et al., 2009). Thepresent study has made it possible to describe short-term changes inneurocognitive functioning during amajor depressive episode. The per-sistence of cognitive deficits that we observed could be partly attribut-able to the severe and recurrent course of the patients' illness, which isgenerally associated with poorer neurocognitive functioning (Fleminget al., 2004; McDermott and Ebmeier, 2009; Swann et al., 2009).

4.4. Clinical implications

The fact that the symptomatology, psychosocial functioning andneurocognitive profile were comparable among the MDD and BDpatients enrolled in the present study suggests that severe and complexcases of major depression and bipolar disorder refer to a similar clinicalreality. The results revealed that a depressive episode is characterizedby occupational, relational and social difficulties which persist despitethe improvement of the depressive symptomatology. Considering thatfunctional deficits are as intense in the syndromal and subsyndromalphases of depression (Marangell et al., 2009), rapid achievement ofcomplete remission should be the primary objective of managementso as to maximize benefits and limit impacts on daily functioning. Tothat end, appropriate medication should be offered in combinationwith psychosocial interventions, including psychoeducation and psy-chotherapy. Such support is also known to improve both depressivesymptoms and psychosocial functioning (Mansell et al., 2005; Parikhet al., 2009). Anxiety symptomatology should be considered in treat-ment management in order to obtain better outcomes.

4.5. Limitations

Our results must be interpreted with caution in view of severalmethodological limitations. Indeed, the generalizability of the resultsis limited by certain factors. As all patients were moderately toseverely depressed and treated in a specialized service, the findingscannot be generalized to larger community samples. Moreover, therelatively small sample size limits statistical analyses and can involvea lack of statistical power of the analysis. In addition, the duration ofthe follow-up was fairly short so that depression could be observedthroughout all of its phases.

It should also be noted that we did not control for the possibleeffects of medication on test performances. However, there is no con-sensus about the effect of medication on cognition (MacQueen andYoung, 2003). Cognitive deficits observed should be considered as a

consequence of cerebral dysfunctioning rather than a main effect ofmedication (Phillips et al., 2008). In brief, we cannot definitively ruleout the possibility of treatment effects on neurocognitive functioning.

4.6. Conclusion

In the case of severe and complex mood disorders, psychosocialand neurocognitive functioning seem similar among MDD and BDdepressed patients. While psychosocial functioning has improvedduring the follow-up, neurocognitive profile remained relatively stableover time. After 1 year of treatment, psychosocial and cognitive deficitspersisted, for most patients, sufficiently to alter daily functioning.

Acknowledgments

This study was supported in part by grants from Janssen-Ortho.However, Janssen-Ortho had no further role in study design; in thecollection, analysis and interpretation of data; in the writing of thereport; and in the decision to submit the paper for publication.

All authors designed the study and wrote the protocol. Julie Godardmanaged the literature searches and undertook the statistical analysis.She also wrote the first draft of the manuscript. All authors contributedto and have approved the final manuscript.

We especially thank Marie-Eve Roussel for her assistance with thestatistical analyses.

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