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Neurocognition and psychosocial functioning in adolescents with bipolar disorder
Journal of Affective Disorders 207 (2017) 406–412
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Journal of Affective Disorders journal homepage: www.elsevier.com/locate/jad
Neurocognition and psychosocial functioning in adolescents with bipolar disorder
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Michael W. Besta, Christopher R. Bowiea, Melanie R. Naibergb, Dwight F. Newtonb, ⁎ Benjamin I. Goldsteinb, a b
Department of Psychology, Queen's University, Kingston, ON, Canada Department of Psychiatry, Sunnybrook Health Sciences Centre, Toronto, ON, Canada
A R T I C L E I N F O
A BS T RAC T
Keywords: Adolescent bipolar disorder Psychosocial functioning Neurocognition Mood
Background: Adults with bipolar disorder demonstrate significantly poorer psychosocial functioning and neurocognition compared to controls. In adult bipolar disorder neurocognition predicts a substantial portion of variance in functioning. Adolescents with bipolar disorder have reducedpsychosocial functioning, but less is known about neurocognitive impairments, and no studies have examined the relationship between neurocognition and functioning in an adolescent sample. Methods: 38 adolescents with bipolar disorder and 49 healthy controls under 20 years of age completed assessments of psychosocial functioning, neurocognitive ability, and psychiatric symptoms. Results: Adolescents with bipolar disorder had significantly poorer psychosocial functioning in domains of daily activities, social functioning, and satisfaction with functioning, ps < .006, compared to healthy controls. They also had poorer general neurocognitive functioning than controls, p=.004, with the greatest impairment on a test of sustained attention. Neurocognition was not a significant predictor of psychosocial functioning in this sample, but depressive symptoms significantly predicted functioning in all domains, p < .033. Limitations: Limited sample size did not allow for complex statistical analyses. Differences in demographic characteristics of the clinical and control groups may limit generalization of these results. Conclusions: This adolescent sample with bipolar disorder experiences significantly poorer neurocognitive and psychosocial functioning compared to controls; however, psychosocial functioning appears to be more strongly related to mood symptoms than to neurocognition. Future work is needed to delineate the time course of neurocognitive functioning and its relation to psychosocial functioning across the course of illness. Adolescence may provide an ideal time for cognitive enhancement and intensive psychosocial intervention.
1. . Introduction Bipolar disorder is associated with various measures of functional disability, including increased health care costs (Simon, 2003), higher unemployment rates (Coryell et al., 1993; Tse and Walsh, 2001), higher dependence on public assistance (Judd and Akiskal, 2003), lower annual income (Goetzel et al., 2003), decreased work productivity (Goetzel et al., 2003), poorer social functioning (Morriss et al., 2007), poorer overall functioning (Goldberg et al., 1995; Keck et al., 1998; Judd et al., 2005), and lower quality of life (Vojta et al., 2001). Given the degree of functional disability associated with the disorder, definitions of recovery now include improvement to normative levels of psychosocial functioning (Harvey, 2005; Grunze et al., 2013). Unfortunately, reviews estimate that up to 60% of individuals with bipolar disorder will not achieve full functional recovery (MacQueen ⁎
et al., 2001). Consequently, greater efforts are being made to understand the nature of functional disability in bipolar disorder, and these domains of functioning have become important treatment targets. Psychosocial functioning appears to be significantly impaired in individuals who are in acute depressive or manic / hypomanic episodes (Rosa et al., 2010; Malhi et al., 2007); depressive symptoms induce the most enduring functional deficits (Simonsen et al., 2010). However, functional impairments persist even after significant mood symptoms have remitted (Andreou and Bozikas, 2013). In samples of euthymic adults, subclinical depressive symptoms continue to be associated with poorer functioning (Baş et al., 2015; Bonnin et al., 2010, 2012), however other factors must also be considered. In fact, although depressive symptoms relate to a person's psychosocial functioning, a better predictor of community function is neurocognitive ability (Wingo et al., 2009; Andreou and Bozikas, 2013). Generally, adults
Correspondence to: Sunnybrook Health Sciences Centre, 2075 Bayview Ave. Room FG 53, Canada. E-mail address: [email protected] (B.I. Goldstein).
http://dx.doi.org/10.1016/j.jad.2016.09.063 Received 21 June 2016; Received in revised form 6 August 2016; Accepted 5 September 2016 Available online 11 October 2016 0165-0327/ © 2016 Elsevier B.V. All rights reserved.
Journal of Affective Disorders 207 (2017) 406–412
M.W. Best et al.
oxidative stress and vascular function as biomarkers of neurocognition in adolescent bipolar disorder, in which we have reported relationships between executive functioning and several traditional cardiovascular risk factors (Naiberg, 2014). The current report has three main aims: 1) to examine psychosocial functioning in adolescents with bipolar disorder compared to healthy controls; 2) to examine neurocognitive ability in adolescents with bipolar disorder relative to healthy controls; 3) to determine how neurocognition is related to psychosocial functioning in adolescent bipolar disorder.
with bipolar disorder demonstrate significantly poorer cognitive functioning in most domains compared to healthy controls (Robinson et al., 2006), and it appears that neurocognition is the best predictor of community functioning (Bowie et al., 2010; Depp et al., 2012; Tse et al., 2014). When both mood symptoms and neurocognition are considered, mood only has a modest direct relationship with functioning (Bowie et al., 2010). Global neurocognition is often reported as predicting community functioning (Bowie et al., 2010; Depp et al., 2012; Andreou and Bozikas, 2013), however, relationships with specific cognitive domains have also been reported: verbal memory and executive functioning (Wingo et al., 2009; Tse et al., 2014), attention (Andreou and Bozikas, 2013; Wingo et al., 2009), and processing speed (Wingo et al., 2009). Similar to functional impairments, neurocognitive difficulties persist into periods of euthymia (Goswami et al., 2006), and appear to have only modest relationships with mood state (Kurtz and Gerraty, 2009), perhaps explaining why reduction in mood symptoms with psychopharmacological treatments often has little effect on everyday functioning. Despite the robust literature in adults demonstrating the real-life importance of this topic, there is a paucity of data among youth with bipolar disorder. Geller et al. (2000) found that over half of the adolescents with bipolar disorder in their sample were functioning poorly, and that they were more impaired than adolescents with attention-deficit / hyperactivity disorder (ADHD) and healthy controls in social, family, and academic functioning. Global functional impairments are consistently reported across samples of adolescents with bipolar disorder (Lewinsohn et al., 1995; Biederman et al., 2005; Wilens et al., 2003) and tend to be paired with lower subjective quality of life (Rademacher et al., 2007). Specific impairments in social and interpersonal functioning are also reported (Wilens et al., 2003; Goldstein et al., 2006) and may be a primary reason why adolescents enter treatment initially. Similar to adult bipolar disorder (Fagiolini et al., 2005; Morriss, 2002), these impairments in psychosocial functioning persist despite remission of significant mood symptoms, however, they tend to worsen during periods of symptom exacerbation (Goldstein et al., 2009). Considering the serious functional consequences of adolescentonset bipolar disorder and the relationship found between neurocognition and functioning in adults, research has begun to examine neurocognition in adolescents with the illness. Initial studies in this area suggest that the general profile of cognitive abilities in adolescents appears to be qualitatively different than that observed in adults with bipolar disorder where a generalized neurocognitive deficit appears to be present. In adolescents, neurocognitive difficulties appear to be more specific. Compared to healthy controls, studies have suggested that adolescents with bipolar disorder have significantly poorer neurocognitive abilities compared to controls in domains of attentional setshifting and visuospatial memory (Dickstein et al., 2004); sustained attention, working memory, and processing speed (Doyle et al., 2005); and verbal declarative memory (Glahn et al., 2005); however, other studies have suggested that adolescents with bipolar disorder may have intact cognitive functions (DelBello et al., 2004). Meta-analyses have attempted to determine the nature of neurocognitive functioning in adolescent bipolar disorder, with similarly inconsistent results. Most studies find reduced verbal memory abilities (Joseph et al., 2008; Horn et al., 2011; Frías et al., 2014). Working memory and visuo-spatial memory also appear to be significantly poorer compared to healthy controls, but to a lesser extent than verbal memory (Joseph et al., 2008; Horn et al., 2011; Frías et al., 2014). It has also been suggested that adolescents with bipolar disorder have poorer executive functioning (Joseph et al., 2008), processing speed (Frías et al., 2014), and social cognition (Frías et al., 2014); however, these findings are not consistent across meta-analyses. This report is the first, to our knowledge, to examine the relationships between neurocognition and psychosocial functioning in adolescents with bipolar disorder, and is part of a broader study examining
2. Method 2.1. Participants Thirty-eight adolescents with bipolar disorder (9 bipolar I, 17 bipolar II, 12 bipolar NOS) were recruited from the Youth Psychiatry Division of Sunnybrook Health Sciences Centre, and 49 psychiatrically healthy controls were recruited from the surrounding community. Bipolar disorder diagnoses were confirmed by experienced clinicians using the Schedule for Affective Disorders and Schizophrenia for School Age Children, Present and Life Version (K-SADS-PL; Kaufman et al., 1997). Healthy control participants were excluded if they had a history of mood or psychotic disorders, alcohol or drug dependence in the past 3 months, history of an anxiety disorder in the past 3 months, or first or second degree relatives with a bipolar or psychotic disorder. Demographic characteristics of the sample are presented in Table 1. There were equal numbers of males and females in the two groups; however, despite attempts to match based on age, the bipolar diagnosis group was significantly older on average than the healthy control group.
Table 1 Demographic characteristics of adolescents with bipolar disorder and healthy controls. Bolded values indicate a significant difference between groups.
Age (Mean SD) Gender (n) (females:males) WASI IQ (Mean SD) K-SADS Mania Rating Scale – Current (Mean SD) K-SADS Depression Rating Scale – Current (Mean SD) K-SADS Mania Rating Scale – Past (Mean SD) K-SADS Depression Rating Scale – Past (Mean SD) Duration of Illness (years) (Mean SD) Lifetime AntiDepressant Medication(n) Lifetime Lithium(n) Lifetime Antipsychotic Medication (n) First Degree Relative with Mood Disorder (n)
407
Bipolar Disorder (n=38)
Healthy Controls (n=49)
Test Statistic
p value
17.42 (1.82) 23: 15
15.96 (1.75) 23: 26
t=3.81 χ2=1.59
p < .001 p=.208
104.21 (13.19) 11.39 (12.28)
110.04 (12.97) .41 (1.19)
t=2.06
p=.042
t=6.24
p < .001
15.41 (10.33)
.46 (1.22)
t=9.96
p < .001
28.45 (11.75)
2.00 (10.07)
t=11.30
p < .001
30.11 (13.54)
2.73 (13.03)
t=9.44
p < .001
6.55 (4.45)
–
–
–
8
1
χ2=8.34
p=.004
9 29
0 0
χ2=12.94 χ2=56.09
p < .001 p < .001
21
3
χ2=27.92
p < .001
Journal of Affective Disorders 207 (2017) 406–412
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total number of correct responses and is a measure of the participant's efficiency in completing the task. Higher scores indicate better performance. The Stockings of Cambridge Task (SOC) is a measure of executive functioning that involves participants moving 3 coloured balls from one location to another in order to match a template. The task consists of 12 trials that become progressively more difficult, requiring an increasing number of moves to match the template. The primary outcome measure was the number of problems the participant solved in the minimum number of moves. Higher scores indicate better performance.
2.2. Measures 2.2.1. Symptom assessment Present and lifetime diagnostic status was evaluated using the Schedule for Affective Disorders and Schizophrenia for School Age Children, Present and Life Version (K-SADS-PL; Kaufman et al., 1997). The K-SADS-PL is a semi-structured interview designed to ascertain present episode and lifetime history of psychiatric illness, according to the Diagnostic and Statistical Manual for Mental Disorders – 4th Edition (APA, 2000) criteria for children and adolescents between 7 and 18 years of age. The K-SADS Mania Rating Scale (K-SADS MRS; Axelson et al., 2003) was used to assess the severity of manic and psychotic symptoms in a continuous manner. The K-SADS MRS is a clinical rating scale that consists of 13 items rated on a 6-point scale from 1=Not present, to 6=Extreme severity. The Depression section of the K-SADS-Present Episode Version (KSADS-Dep 12; Ambrosini et al., 1989) was used to assess the severity of depressive symptoms in a continuous manner. The K-SADS-Dep 12 is a clinical rating scale consisting of 12 items rated on a 6 point scale from 1=Not present, to 6=Extreme severity.
2.3. Procedure The current report is part of a larger study on oxidative stress and vascular measures as biomarkers of neurocognition in adolescent bipolar disorder. This study received ethics clearance through the Research Ethics Board of Sunnybrook Health Sciences Centre. 2.4. Data analysis 2.4.1. Psychosocial functioning To examine differences in psychosocial functioning between adolescents with bipolar disorder and healthy control participants, LIFE scores were examined. The LIFE scales were split into 3 sub-domain scores: Daily Functioning (comprising academic impairment, impairment in household activities, and enjoyment in recreational activities), Social Functioning (comprising relationships with parents, siblings, and friends), and subjective satisfaction with overall functioning (using the satisfaction with functioning item). Daily Functioning and Social Functioning were calculated as the mean of the standardized scores of the scales comprising them. ANCOVAs were conducted to compare groups on these three scores controlling for age since it is theoretically likely that age would influence a person's opportunity to have reached functional milestones and there was a significant age difference between groups.
2.2.2. Psychosocial functioning The Longitudinal Interval Follow-up Evaluation (LIFE; Keller et al., 1987) was used to assess psychosocial functioning. The LIFE is a semistructured interview that can provide both cross-sectional and longitudinal information on the functioning of children and adolescents. The LIFE covers domains of psychosocial functioning including work, academics, household activities, interpersonal relationships, recreational activities, and overall life satisfaction. Higher scores indicate more impairment in functioning. 2.2.3. Family history To determine whether children had a first or second degree relative with a psychiatric illness, the Family History Screen (Weissman et al., 2000) was conducted with the adolescent and parent/s. 2.2.4. Neurocognition To provide an estimate of general intelligence, all participants were administered the Weschler Abbreviated Scale of Intelligence (WASI; Wechsler, 1999). To assess specific domains of neurocognition, selected tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB) were used. CANTAB eclipse version 2.0 (Cambridge Cognition, Ltd., 2005) was used in the current study. The CANTAB is administered on a touch-sensitive computer screen to facilitate participant responding. The Rapid Visual Information Processing Task (RVP) is a test of sustained attention in which numerical digits are serially presented to the participant. The participant must respond every time they see one of three target sequences of numbers. The primary outcome measure was a signal detection measure of target sensitivity that compares the probability of a response to a target (hit) to the probability of a response to a non-target (false alarm). Higher scores indicate better performance. The Spatial Span Task (SSP) assesses visual working memory capacity. Participants are shown a screen of white squares, some of which briefly change colour in a variable sequence. Participants must then touch the squares that changed colour in the same order that they changed colour in. The number of squares changing colour increases as the task progresses. The primary outcome measure was the total number of items correct. Higher scores indicate better performance. To assess executive functioning, the Intra/Extra Dimensional Shift Task (IED) was used which consists of different pairs of stimuli that are reinforced according to an implicit rule that the participant must learn. The reinforcement rule then changes, and the participant must flexibly adapt and learn the new rule. The primary outcome measure was the
2.4.2. Neurocognition To examine differences in neurocognition between adolescents with bipolar disorder and healthy control participants, we examined full scale IQ from the WASI and a neurocognitive composite score. The neurocognitive composite score was calculated as the mean of the standardized scores from the primary dependent variables of the SSP, RVP, IED, and SOC. Standardized scores for each test were calculated based on CANTAB norms stratified by age. Full scale IQ and the neurocognitive composite score were compared between groups using independent samples t-tests. To follow-up the main neurocognitive composite analysis, each neurocognitive test was also examined separately post-hoc, in an attempt to examine domain specific impairments in adolescent bipolar disorder. A Bonferroni correction was applied to these analyses such that the new critical p value was set at p=.013 (.05/4). Additionally, relationships between neurocognition, duration of illness, and medication were examined using a pearson correlation (neurocognition with duration of illness) and a pointbiserial correlation (neurocognition with medication) to determine the impact of disease characteristics on neurocognition. 2.4.3. Predicting psychosocial functioning The relationships of global neurocognition, depressive symptoms, and manic symptoms with psychosocial functioning were examined. Neurocognition has been found to be the best predictor of functioning in adult populations, however, to our knowledge this relationship has never been reported in adolescent bipolar disorder. To examine these relationships, simultaneous regression analyses were used with neurocognitive ability, depressive symptoms, and manic symptoms, predicting the 3 domains of psychosocial functioning (Daily, Social, and 408
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Table 2 Global neurocognition, depressive symptoms, and manic symptoms predicting daily functioning, social functioning, and satisfaction with functioning.
Daily Functioning Neurocognition K-SADS Depression K-SADS Mania Social Functioning Neurocognition K-SADS Depression K-SADS Mania Satisfaction with Functioning Neurocognition K-SADS Depression K-SADS Mania
Fig. 1. Mean (SE) psychosocial functioning in healthy controls and adolescents with bipolar disorder controlling for age.
Satisfaction).
β
t-value
p-value
−.043 .434 −.044
−.305 2.331 −.236
.762 .026 .815
.220 .265 −.124
1.28 1.36 −.632
.210 .183 .532
Variance Accounted for by Model (R2) .176
.100
.505 .070 .797 −.467
.539 5.460 −3.186
.594 < .001 .003
Note: Bolded values indicate p < .05.
3. Results
illness, r=−.21, p=.33, anti-depressant medication use, r=−.09, p=.61, or antipsychotic medication use, r=−.15, p=.38.
3.1. Psychosocial functioning On the LIFE evaluation of psychosocial functioning, compared to healthy controls, adolescents with bipolar disorder were rated as having significantly poorer daily functioning, F(1,83)=43.21, p < .001, partial η2=.342, social functioning, F(1,83)=19.93, p < .001, partial η2=.194, and less satisfaction with functioning, F(1,82)=21.49, p < .001, partial η2=.208 (see Fig. 1).
3.3. Predicting psychosocial functioning Results of the regression analyses predicting domains of psychosocial functioning are presented in Table 2. Depressive symptoms were a significant predictor of daily functioning and satisfaction. Manic symptoms significantly predicted satisfaction with functioning but not daily or social functioning. Neurocognition was not a significant predictor of any domain of psychosocial functioning. For exploratory purposes, all individual domains of neurocognition were entered into regression analyses predicting each domain of functioning. No neurocognitive domains significantly predicted functioning (Table 3).
3.2. Neurocognition On the WASI Full Scale IQ estimate, adolescents with bipolar disorder (M=104.21, SD=13.19) had significantly lower IQs than healthy control participants (M=110.04, SD=12.97), t(85)=2.06, p=.042. Adolescents with bipolar disorder (M=−.182, SD=.647) also had significantly lower scores on the neurocognitive composite score than healthy control participants (M=.151, SD=.538), t(84)=2.98, p=.011. Results from the individual CANTAB tasks are presented in Fig. 2. Adolescents with bipolar disorder only performed significantly worse than healthy control participants in the domain of sustained attention, as measured by the Rapid Visual Information Processing Task, p=.006, d=.735, however all domains in this small sample were in the direction of adolescents with bipolar disorder performing more poorly than healthy controls, with effect sizes ranging from d=.09 to d=.62. Neurocognition was not significantly correlated with duration of
3.4. Supplementary analyses Due to the significant difference in WASI full scale IQ between groups, we also ran all of the above analyses including WASI IQ as a covariate. All results remained unchanged. Table 3 Individual neurocognitive tests predicting daily functioning, social functioning, and satisfaction with functioning.
Daily Functioning Spatial Span Rapid Visual Processing Intra/Extra Dimensional Shift Stockings of Cambridge Social Functioning Spatial Span Rapid Visual Processing Intra/Extra Dimensional Shift Stockings of Cambridge Satisfaction with Functioning Spatial Span Rapid Visual Processing Intra/Extra Dimensional Shift Stockings of Cambridge
Fig. 2. Mean (SE) neurocognitive subtest performance in healthy controls and adolescents with bipolar disorder. Cohen's d is presented for each comparison.
409
β
t-value
p-value
.228 −.297 −.195
1.20 −1.55 −1.01
.242 .134 .324
.139
.71
.482
.239 .236 −.143
1.26 1.23 −.73
.220 .232 .467
.193
.99
.330
Variance Accounted for by Model (R2) .162
.160
.223 .207 −.252 −.242
1.11 −1.32 −1.25
.277 .200 .226
.366
1.91
.069
Journal of Affective Disorders 207 (2017) 406–412
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Bipolar disorders that onset prior to the age of 18 are associated with a more chronic course of illness and greater functional impairment later in life (Perlis et al., 2004), suggesting that early intervention may be critical to preventing the functional decline typically associated with the illness. Early psychosocial and pharmacological intervention for depressive symptoms may be critical to improving psychosocial functioning for adolescents with bipolar disorder. Adolescence may also provide an ideal point for cognitive enhancement (e.g. through the use of cognitive remediation techniques; Wykes et al., 2011), before neurocognitive impairments worsen and become more critical for independent functioning. Cognitive remediation has demonstrated efficacy in schizophrenia (Wykes et al., 2011), adult bipolar disorder (Deckersbach et al., 2010), and more recently in major depressive disorder (Bowie et al., 2013a, 2013b). Recently cognitive remediation has received attention as a potentially important treatment modality for adolescents with bipolar disorder to improve cognitive and psychosocial functioning (Dickstein et al., 2015). Aerobic exercise has also been demonstrated to enhance cognitive function among healthy adults (Hillman et al., 2008), and appears to be an important cognitive enhancing strategy in adolescents with bipolar disorder (Metcalfe et al., 2016). Adolescence is a critical period of neurodevelopment, during which time cognitive enhancement has the potential to generate lasting changes for later development. For individuals who develop bipolar disorder during this period, enhancement of cognition may provide a route to reducing functional impairment experienced later in life. This study should be interpreted with consideration of several limitations. First, the sample size does not afford sufficient power to undertake complex statistical analyses. It is possible that this study was underpowered to detect some significant effects, especially in the regression analyses. Longitudinal studies with larger samples should examine relationships across time between neurocognition and functioning. Due to the automated nature of the assessment, the cognitive assessment battery that was employed did not contain a measure of verbal memory, typically found to be the most impaired cognitive domain in both adults and adolescents with bipolar disorder (Joseph et al., 2008; Horn et al., 2011; Frías et al., 2014). Verbal memory may also be the cognitive domain that is most functionally relevant, and thus an assessment package containing a measure of verbal memory may find significant relationships between neurocognition and functioning. Healthy control participants had an average IQ that was almost one standard deviation above the normative average, indicating that the current differences between healthy controls and adolescents with bipolar disorder may not be generalizable when comparing to a more representative healthy control population. Additionally, the healthy control participants were significantly younger than the participants with bipolar disorder. Although we corrected for age in our analyses, increasing age provides greater opportunities for cognitive and functional skill development, therefore it is possible that the current results are an underestimation of the difficulties adolescents with bipolar disorder have.
4. Discussion The present study examined neurocognition and psychosocial functioning among adolescents with bipolar disorder and was the first study to our knowledge to examine the relationship between neurocognition and functioning in this population. Compared to healthy controls, adolescents with bipolar disorder demonstrated poorer psychosocial functioning in domains of daily activities, social functioning, and satisfaction with their functioning. Adolescents with bipolar disorder also displayed poorer global neurocognition than controls, with the greatest impairment in the domain of visual sustained attention. Contrary to our hypotheses, neurocognition was not a significant predictor of psychosocial functioning; depressive symptoms had the strongest relationships with functioning. In the current sample, we found similar psychosocial functioning impairments as those found in previous reports on adolescents with bipolar disorder (e.g. Goldstein et al. (2009)). We also observed poorer cognitive functioning than healthy controls, similar to results observed in adults with bipolar disorder (Robinson et al., 2006). The differences in cognition were statistically significant for the composite score and for sustained attention, but the level of impairment would be considered to be in the mild range for sustained attention, working memory, and executive functions. Duration of illness and number of mood episodes is associated with cognitive impairment in adult bipolar disorder (Martínez-Arán et al., 2004), making the longitudinal trajectory of cognitive functions as adolescents with bipolar disorder emerge into adulthood, an area in need of attention. We had hypothesized that the relationship between neurocognition and psychosocial functioning would be similar to that observed in adults with bipolar disorder, in which cognitive abilities are consistently found to be the best predictor of functional abilities (Bowie et al., 2010; Depp et al., 2012; Tse et al., 2014). However, in contrast to our hypothesis, neurocognition was not a significant predictor of psychosocial functioning for these adolescents. In fact, depressive symptoms were the only consistent predictor across domains of functioning. It is possible that this relationship was not significant due to the relatively small sample size, though the effect sizes were quite small. An alternative explanation is that at this early stage in the illness, neurocognitive abilities are less impaired and less functionally relevant. For example, there is evidence that bipolar disorder is associated with overachievement during adolescence (MacCabe et al., 2010) despite significantly poorer general intelligence than healthy controls (Vreeker et al., 2016). In addition to academics, we can consider the life demands and our ability to measure functional difficulties fundamentally different in adolescence compared to adulthood. In adulthood, functioning measures tap into skills that are typically performed with independence and with a broader range of consequences. The ecology of adolescents is characterized by structures and consequences imposed by family and school; these may buffer functioning, making neurocognitive ability less directly relevant for functioning during that time period. Symptoms contributing to withdrawal from these structural supports, such as depressive symptoms, may be more relevant for functioning during adolescence, but neurocognitive symptoms may become more important as structural supports diminish in adulthood and responsibility for functioning transitions to a greater extent onto the individual. While neurocognition was not related to psychosocial functioning in this sample, current depressive symptoms were related to daily functioning and satisfaction with functioning. This raises the question of whether neurocognition and functioning are a function of mood state or whether they are stable across mood states. In adults, there is compelling evidence that difficulties persist even in states of euthymia (Martínez-Arán et al., 2004), and there is some evidence that the same is true in adolescent bipolar disorder (Pavuluri et al., 2006). Clinically, depressive symptoms appear to be the most important treatment target to improve psychosocial functioning in adolescent bipolar disorder.
5. Conclusion Adolescents with bipolar disorder demonstrate poorer neurocognitive and psychosocial functioning compared to healthy controls. Contrasting multiple prior studies of adults, neurocognition was not a significant predictor of functioning in this small sample; depressive symptoms were the only consistent predictor across domains of functioning. Treatment of depressive symptoms at this age will be important, but adolescence may also provide an opportunity to enhance neurocognitive abilities necessary for functioning as adolescents emerge into adulthood. More research on the relationship between neurocognition and psychosocial functioning in this age group is necessary, as well as examinations of cognitive enhancement for improving neurocognition in this age group. 410
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Contents lists available at ScienceDirect
Journal of Affective Disorders journal homepage: www.elsevier.com/locate/jad
Neurocognition and psychosocial functioning in adolescents with bipolar disorder
crossmark
Michael W. Besta, Christopher R. Bowiea, Melanie R. Naibergb, Dwight F. Newtonb, ⁎ Benjamin I. Goldsteinb, a b
Department of Psychology, Queen's University, Kingston, ON, Canada Department of Psychiatry, Sunnybrook Health Sciences Centre, Toronto, ON, Canada
A R T I C L E I N F O
A BS T RAC T
Keywords: Adolescent bipolar disorder Psychosocial functioning Neurocognition Mood
Background: Adults with bipolar disorder demonstrate significantly poorer psychosocial functioning and neurocognition compared to controls. In adult bipolar disorder neurocognition predicts a substantial portion of variance in functioning. Adolescents with bipolar disorder have reducedpsychosocial functioning, but less is known about neurocognitive impairments, and no studies have examined the relationship between neurocognition and functioning in an adolescent sample. Methods: 38 adolescents with bipolar disorder and 49 healthy controls under 20 years of age completed assessments of psychosocial functioning, neurocognitive ability, and psychiatric symptoms. Results: Adolescents with bipolar disorder had significantly poorer psychosocial functioning in domains of daily activities, social functioning, and satisfaction with functioning, ps < .006, compared to healthy controls. They also had poorer general neurocognitive functioning than controls, p=.004, with the greatest impairment on a test of sustained attention. Neurocognition was not a significant predictor of psychosocial functioning in this sample, but depressive symptoms significantly predicted functioning in all domains, p < .033. Limitations: Limited sample size did not allow for complex statistical analyses. Differences in demographic characteristics of the clinical and control groups may limit generalization of these results. Conclusions: This adolescent sample with bipolar disorder experiences significantly poorer neurocognitive and psychosocial functioning compared to controls; however, psychosocial functioning appears to be more strongly related to mood symptoms than to neurocognition. Future work is needed to delineate the time course of neurocognitive functioning and its relation to psychosocial functioning across the course of illness. Adolescence may provide an ideal time for cognitive enhancement and intensive psychosocial intervention.
1. . Introduction Bipolar disorder is associated with various measures of functional disability, including increased health care costs (Simon, 2003), higher unemployment rates (Coryell et al., 1993; Tse and Walsh, 2001), higher dependence on public assistance (Judd and Akiskal, 2003), lower annual income (Goetzel et al., 2003), decreased work productivity (Goetzel et al., 2003), poorer social functioning (Morriss et al., 2007), poorer overall functioning (Goldberg et al., 1995; Keck et al., 1998; Judd et al., 2005), and lower quality of life (Vojta et al., 2001). Given the degree of functional disability associated with the disorder, definitions of recovery now include improvement to normative levels of psychosocial functioning (Harvey, 2005; Grunze et al., 2013). Unfortunately, reviews estimate that up to 60% of individuals with bipolar disorder will not achieve full functional recovery (MacQueen ⁎
et al., 2001). Consequently, greater efforts are being made to understand the nature of functional disability in bipolar disorder, and these domains of functioning have become important treatment targets. Psychosocial functioning appears to be significantly impaired in individuals who are in acute depressive or manic / hypomanic episodes (Rosa et al., 2010; Malhi et al., 2007); depressive symptoms induce the most enduring functional deficits (Simonsen et al., 2010). However, functional impairments persist even after significant mood symptoms have remitted (Andreou and Bozikas, 2013). In samples of euthymic adults, subclinical depressive symptoms continue to be associated with poorer functioning (Baş et al., 2015; Bonnin et al., 2010, 2012), however other factors must also be considered. In fact, although depressive symptoms relate to a person's psychosocial functioning, a better predictor of community function is neurocognitive ability (Wingo et al., 2009; Andreou and Bozikas, 2013). Generally, adults
Correspondence to: Sunnybrook Health Sciences Centre, 2075 Bayview Ave. Room FG 53, Canada. E-mail address: [email protected] (B.I. Goldstein).
http://dx.doi.org/10.1016/j.jad.2016.09.063 Received 21 June 2016; Received in revised form 6 August 2016; Accepted 5 September 2016 Available online 11 October 2016 0165-0327/ © 2016 Elsevier B.V. All rights reserved.
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oxidative stress and vascular function as biomarkers of neurocognition in adolescent bipolar disorder, in which we have reported relationships between executive functioning and several traditional cardiovascular risk factors (Naiberg, 2014). The current report has three main aims: 1) to examine psychosocial functioning in adolescents with bipolar disorder compared to healthy controls; 2) to examine neurocognitive ability in adolescents with bipolar disorder relative to healthy controls; 3) to determine how neurocognition is related to psychosocial functioning in adolescent bipolar disorder.
with bipolar disorder demonstrate significantly poorer cognitive functioning in most domains compared to healthy controls (Robinson et al., 2006), and it appears that neurocognition is the best predictor of community functioning (Bowie et al., 2010; Depp et al., 2012; Tse et al., 2014). When both mood symptoms and neurocognition are considered, mood only has a modest direct relationship with functioning (Bowie et al., 2010). Global neurocognition is often reported as predicting community functioning (Bowie et al., 2010; Depp et al., 2012; Andreou and Bozikas, 2013), however, relationships with specific cognitive domains have also been reported: verbal memory and executive functioning (Wingo et al., 2009; Tse et al., 2014), attention (Andreou and Bozikas, 2013; Wingo et al., 2009), and processing speed (Wingo et al., 2009). Similar to functional impairments, neurocognitive difficulties persist into periods of euthymia (Goswami et al., 2006), and appear to have only modest relationships with mood state (Kurtz and Gerraty, 2009), perhaps explaining why reduction in mood symptoms with psychopharmacological treatments often has little effect on everyday functioning. Despite the robust literature in adults demonstrating the real-life importance of this topic, there is a paucity of data among youth with bipolar disorder. Geller et al. (2000) found that over half of the adolescents with bipolar disorder in their sample were functioning poorly, and that they were more impaired than adolescents with attention-deficit / hyperactivity disorder (ADHD) and healthy controls in social, family, and academic functioning. Global functional impairments are consistently reported across samples of adolescents with bipolar disorder (Lewinsohn et al., 1995; Biederman et al., 2005; Wilens et al., 2003) and tend to be paired with lower subjective quality of life (Rademacher et al., 2007). Specific impairments in social and interpersonal functioning are also reported (Wilens et al., 2003; Goldstein et al., 2006) and may be a primary reason why adolescents enter treatment initially. Similar to adult bipolar disorder (Fagiolini et al., 2005; Morriss, 2002), these impairments in psychosocial functioning persist despite remission of significant mood symptoms, however, they tend to worsen during periods of symptom exacerbation (Goldstein et al., 2009). Considering the serious functional consequences of adolescentonset bipolar disorder and the relationship found between neurocognition and functioning in adults, research has begun to examine neurocognition in adolescents with the illness. Initial studies in this area suggest that the general profile of cognitive abilities in adolescents appears to be qualitatively different than that observed in adults with bipolar disorder where a generalized neurocognitive deficit appears to be present. In adolescents, neurocognitive difficulties appear to be more specific. Compared to healthy controls, studies have suggested that adolescents with bipolar disorder have significantly poorer neurocognitive abilities compared to controls in domains of attentional setshifting and visuospatial memory (Dickstein et al., 2004); sustained attention, working memory, and processing speed (Doyle et al., 2005); and verbal declarative memory (Glahn et al., 2005); however, other studies have suggested that adolescents with bipolar disorder may have intact cognitive functions (DelBello et al., 2004). Meta-analyses have attempted to determine the nature of neurocognitive functioning in adolescent bipolar disorder, with similarly inconsistent results. Most studies find reduced verbal memory abilities (Joseph et al., 2008; Horn et al., 2011; Frías et al., 2014). Working memory and visuo-spatial memory also appear to be significantly poorer compared to healthy controls, but to a lesser extent than verbal memory (Joseph et al., 2008; Horn et al., 2011; Frías et al., 2014). It has also been suggested that adolescents with bipolar disorder have poorer executive functioning (Joseph et al., 2008), processing speed (Frías et al., 2014), and social cognition (Frías et al., 2014); however, these findings are not consistent across meta-analyses. This report is the first, to our knowledge, to examine the relationships between neurocognition and psychosocial functioning in adolescents with bipolar disorder, and is part of a broader study examining
2. Method 2.1. Participants Thirty-eight adolescents with bipolar disorder (9 bipolar I, 17 bipolar II, 12 bipolar NOS) were recruited from the Youth Psychiatry Division of Sunnybrook Health Sciences Centre, and 49 psychiatrically healthy controls were recruited from the surrounding community. Bipolar disorder diagnoses were confirmed by experienced clinicians using the Schedule for Affective Disorders and Schizophrenia for School Age Children, Present and Life Version (K-SADS-PL; Kaufman et al., 1997). Healthy control participants were excluded if they had a history of mood or psychotic disorders, alcohol or drug dependence in the past 3 months, history of an anxiety disorder in the past 3 months, or first or second degree relatives with a bipolar or psychotic disorder. Demographic characteristics of the sample are presented in Table 1. There were equal numbers of males and females in the two groups; however, despite attempts to match based on age, the bipolar diagnosis group was significantly older on average than the healthy control group.
Table 1 Demographic characteristics of adolescents with bipolar disorder and healthy controls. Bolded values indicate a significant difference between groups.
Age (Mean SD) Gender (n) (females:males) WASI IQ (Mean SD) K-SADS Mania Rating Scale – Current (Mean SD) K-SADS Depression Rating Scale – Current (Mean SD) K-SADS Mania Rating Scale – Past (Mean SD) K-SADS Depression Rating Scale – Past (Mean SD) Duration of Illness (years) (Mean SD) Lifetime AntiDepressant Medication(n) Lifetime Lithium(n) Lifetime Antipsychotic Medication (n) First Degree Relative with Mood Disorder (n)
407
Bipolar Disorder (n=38)
Healthy Controls (n=49)
Test Statistic
p value
17.42 (1.82) 23: 15
15.96 (1.75) 23: 26
t=3.81 χ2=1.59
p < .001 p=.208
104.21 (13.19) 11.39 (12.28)
110.04 (12.97) .41 (1.19)
t=2.06
p=.042
t=6.24
p < .001
15.41 (10.33)
.46 (1.22)
t=9.96
p < .001
28.45 (11.75)
2.00 (10.07)
t=11.30
p < .001
30.11 (13.54)
2.73 (13.03)
t=9.44
p < .001
6.55 (4.45)
–
–
–
8
1
χ2=8.34
p=.004
9 29
0 0
χ2=12.94 χ2=56.09
p < .001 p < .001
21
3
χ2=27.92
p < .001
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total number of correct responses and is a measure of the participant's efficiency in completing the task. Higher scores indicate better performance. The Stockings of Cambridge Task (SOC) is a measure of executive functioning that involves participants moving 3 coloured balls from one location to another in order to match a template. The task consists of 12 trials that become progressively more difficult, requiring an increasing number of moves to match the template. The primary outcome measure was the number of problems the participant solved in the minimum number of moves. Higher scores indicate better performance.
2.2. Measures 2.2.1. Symptom assessment Present and lifetime diagnostic status was evaluated using the Schedule for Affective Disorders and Schizophrenia for School Age Children, Present and Life Version (K-SADS-PL; Kaufman et al., 1997). The K-SADS-PL is a semi-structured interview designed to ascertain present episode and lifetime history of psychiatric illness, according to the Diagnostic and Statistical Manual for Mental Disorders – 4th Edition (APA, 2000) criteria for children and adolescents between 7 and 18 years of age. The K-SADS Mania Rating Scale (K-SADS MRS; Axelson et al., 2003) was used to assess the severity of manic and psychotic symptoms in a continuous manner. The K-SADS MRS is a clinical rating scale that consists of 13 items rated on a 6-point scale from 1=Not present, to 6=Extreme severity. The Depression section of the K-SADS-Present Episode Version (KSADS-Dep 12; Ambrosini et al., 1989) was used to assess the severity of depressive symptoms in a continuous manner. The K-SADS-Dep 12 is a clinical rating scale consisting of 12 items rated on a 6 point scale from 1=Not present, to 6=Extreme severity.
2.3. Procedure The current report is part of a larger study on oxidative stress and vascular measures as biomarkers of neurocognition in adolescent bipolar disorder. This study received ethics clearance through the Research Ethics Board of Sunnybrook Health Sciences Centre. 2.4. Data analysis 2.4.1. Psychosocial functioning To examine differences in psychosocial functioning between adolescents with bipolar disorder and healthy control participants, LIFE scores were examined. The LIFE scales were split into 3 sub-domain scores: Daily Functioning (comprising academic impairment, impairment in household activities, and enjoyment in recreational activities), Social Functioning (comprising relationships with parents, siblings, and friends), and subjective satisfaction with overall functioning (using the satisfaction with functioning item). Daily Functioning and Social Functioning were calculated as the mean of the standardized scores of the scales comprising them. ANCOVAs were conducted to compare groups on these three scores controlling for age since it is theoretically likely that age would influence a person's opportunity to have reached functional milestones and there was a significant age difference between groups.
2.2.2. Psychosocial functioning The Longitudinal Interval Follow-up Evaluation (LIFE; Keller et al., 1987) was used to assess psychosocial functioning. The LIFE is a semistructured interview that can provide both cross-sectional and longitudinal information on the functioning of children and adolescents. The LIFE covers domains of psychosocial functioning including work, academics, household activities, interpersonal relationships, recreational activities, and overall life satisfaction. Higher scores indicate more impairment in functioning. 2.2.3. Family history To determine whether children had a first or second degree relative with a psychiatric illness, the Family History Screen (Weissman et al., 2000) was conducted with the adolescent and parent/s. 2.2.4. Neurocognition To provide an estimate of general intelligence, all participants were administered the Weschler Abbreviated Scale of Intelligence (WASI; Wechsler, 1999). To assess specific domains of neurocognition, selected tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB) were used. CANTAB eclipse version 2.0 (Cambridge Cognition, Ltd., 2005) was used in the current study. The CANTAB is administered on a touch-sensitive computer screen to facilitate participant responding. The Rapid Visual Information Processing Task (RVP) is a test of sustained attention in which numerical digits are serially presented to the participant. The participant must respond every time they see one of three target sequences of numbers. The primary outcome measure was a signal detection measure of target sensitivity that compares the probability of a response to a target (hit) to the probability of a response to a non-target (false alarm). Higher scores indicate better performance. The Spatial Span Task (SSP) assesses visual working memory capacity. Participants are shown a screen of white squares, some of which briefly change colour in a variable sequence. Participants must then touch the squares that changed colour in the same order that they changed colour in. The number of squares changing colour increases as the task progresses. The primary outcome measure was the total number of items correct. Higher scores indicate better performance. To assess executive functioning, the Intra/Extra Dimensional Shift Task (IED) was used which consists of different pairs of stimuli that are reinforced according to an implicit rule that the participant must learn. The reinforcement rule then changes, and the participant must flexibly adapt and learn the new rule. The primary outcome measure was the
2.4.2. Neurocognition To examine differences in neurocognition between adolescents with bipolar disorder and healthy control participants, we examined full scale IQ from the WASI and a neurocognitive composite score. The neurocognitive composite score was calculated as the mean of the standardized scores from the primary dependent variables of the SSP, RVP, IED, and SOC. Standardized scores for each test were calculated based on CANTAB norms stratified by age. Full scale IQ and the neurocognitive composite score were compared between groups using independent samples t-tests. To follow-up the main neurocognitive composite analysis, each neurocognitive test was also examined separately post-hoc, in an attempt to examine domain specific impairments in adolescent bipolar disorder. A Bonferroni correction was applied to these analyses such that the new critical p value was set at p=.013 (.05/4). Additionally, relationships between neurocognition, duration of illness, and medication were examined using a pearson correlation (neurocognition with duration of illness) and a pointbiserial correlation (neurocognition with medication) to determine the impact of disease characteristics on neurocognition. 2.4.3. Predicting psychosocial functioning The relationships of global neurocognition, depressive symptoms, and manic symptoms with psychosocial functioning were examined. Neurocognition has been found to be the best predictor of functioning in adult populations, however, to our knowledge this relationship has never been reported in adolescent bipolar disorder. To examine these relationships, simultaneous regression analyses were used with neurocognitive ability, depressive symptoms, and manic symptoms, predicting the 3 domains of psychosocial functioning (Daily, Social, and 408
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Table 2 Global neurocognition, depressive symptoms, and manic symptoms predicting daily functioning, social functioning, and satisfaction with functioning.
Daily Functioning Neurocognition K-SADS Depression K-SADS Mania Social Functioning Neurocognition K-SADS Depression K-SADS Mania Satisfaction with Functioning Neurocognition K-SADS Depression K-SADS Mania
Fig. 1. Mean (SE) psychosocial functioning in healthy controls and adolescents with bipolar disorder controlling for age.
Satisfaction).
β
t-value
p-value
−.043 .434 −.044
−.305 2.331 −.236
.762 .026 .815
.220 .265 −.124
1.28 1.36 −.632
.210 .183 .532
Variance Accounted for by Model (R2) .176
.100
.505 .070 .797 −.467
.539 5.460 −3.186
.594 < .001 .003
Note: Bolded values indicate p < .05.
3. Results
illness, r=−.21, p=.33, anti-depressant medication use, r=−.09, p=.61, or antipsychotic medication use, r=−.15, p=.38.
3.1. Psychosocial functioning On the LIFE evaluation of psychosocial functioning, compared to healthy controls, adolescents with bipolar disorder were rated as having significantly poorer daily functioning, F(1,83)=43.21, p < .001, partial η2=.342, social functioning, F(1,83)=19.93, p < .001, partial η2=.194, and less satisfaction with functioning, F(1,82)=21.49, p < .001, partial η2=.208 (see Fig. 1).
3.3. Predicting psychosocial functioning Results of the regression analyses predicting domains of psychosocial functioning are presented in Table 2. Depressive symptoms were a significant predictor of daily functioning and satisfaction. Manic symptoms significantly predicted satisfaction with functioning but not daily or social functioning. Neurocognition was not a significant predictor of any domain of psychosocial functioning. For exploratory purposes, all individual domains of neurocognition were entered into regression analyses predicting each domain of functioning. No neurocognitive domains significantly predicted functioning (Table 3).
3.2. Neurocognition On the WASI Full Scale IQ estimate, adolescents with bipolar disorder (M=104.21, SD=13.19) had significantly lower IQs than healthy control participants (M=110.04, SD=12.97), t(85)=2.06, p=.042. Adolescents with bipolar disorder (M=−.182, SD=.647) also had significantly lower scores on the neurocognitive composite score than healthy control participants (M=.151, SD=.538), t(84)=2.98, p=.011. Results from the individual CANTAB tasks are presented in Fig. 2. Adolescents with bipolar disorder only performed significantly worse than healthy control participants in the domain of sustained attention, as measured by the Rapid Visual Information Processing Task, p=.006, d=.735, however all domains in this small sample were in the direction of adolescents with bipolar disorder performing more poorly than healthy controls, with effect sizes ranging from d=.09 to d=.62. Neurocognition was not significantly correlated with duration of
3.4. Supplementary analyses Due to the significant difference in WASI full scale IQ between groups, we also ran all of the above analyses including WASI IQ as a covariate. All results remained unchanged. Table 3 Individual neurocognitive tests predicting daily functioning, social functioning, and satisfaction with functioning.
Daily Functioning Spatial Span Rapid Visual Processing Intra/Extra Dimensional Shift Stockings of Cambridge Social Functioning Spatial Span Rapid Visual Processing Intra/Extra Dimensional Shift Stockings of Cambridge Satisfaction with Functioning Spatial Span Rapid Visual Processing Intra/Extra Dimensional Shift Stockings of Cambridge
Fig. 2. Mean (SE) neurocognitive subtest performance in healthy controls and adolescents with bipolar disorder. Cohen's d is presented for each comparison.
409
β
t-value
p-value
.228 −.297 −.195
1.20 −1.55 −1.01
.242 .134 .324
.139
.71
.482
.239 .236 −.143
1.26 1.23 −.73
.220 .232 .467
.193
.99
.330
Variance Accounted for by Model (R2) .162
.160
.223 .207 −.252 −.242
1.11 −1.32 −1.25
.277 .200 .226
.366
1.91
.069
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Bipolar disorders that onset prior to the age of 18 are associated with a more chronic course of illness and greater functional impairment later in life (Perlis et al., 2004), suggesting that early intervention may be critical to preventing the functional decline typically associated with the illness. Early psychosocial and pharmacological intervention for depressive symptoms may be critical to improving psychosocial functioning for adolescents with bipolar disorder. Adolescence may also provide an ideal point for cognitive enhancement (e.g. through the use of cognitive remediation techniques; Wykes et al., 2011), before neurocognitive impairments worsen and become more critical for independent functioning. Cognitive remediation has demonstrated efficacy in schizophrenia (Wykes et al., 2011), adult bipolar disorder (Deckersbach et al., 2010), and more recently in major depressive disorder (Bowie et al., 2013a, 2013b). Recently cognitive remediation has received attention as a potentially important treatment modality for adolescents with bipolar disorder to improve cognitive and psychosocial functioning (Dickstein et al., 2015). Aerobic exercise has also been demonstrated to enhance cognitive function among healthy adults (Hillman et al., 2008), and appears to be an important cognitive enhancing strategy in adolescents with bipolar disorder (Metcalfe et al., 2016). Adolescence is a critical period of neurodevelopment, during which time cognitive enhancement has the potential to generate lasting changes for later development. For individuals who develop bipolar disorder during this period, enhancement of cognition may provide a route to reducing functional impairment experienced later in life. This study should be interpreted with consideration of several limitations. First, the sample size does not afford sufficient power to undertake complex statistical analyses. It is possible that this study was underpowered to detect some significant effects, especially in the regression analyses. Longitudinal studies with larger samples should examine relationships across time between neurocognition and functioning. Due to the automated nature of the assessment, the cognitive assessment battery that was employed did not contain a measure of verbal memory, typically found to be the most impaired cognitive domain in both adults and adolescents with bipolar disorder (Joseph et al., 2008; Horn et al., 2011; Frías et al., 2014). Verbal memory may also be the cognitive domain that is most functionally relevant, and thus an assessment package containing a measure of verbal memory may find significant relationships between neurocognition and functioning. Healthy control participants had an average IQ that was almost one standard deviation above the normative average, indicating that the current differences between healthy controls and adolescents with bipolar disorder may not be generalizable when comparing to a more representative healthy control population. Additionally, the healthy control participants were significantly younger than the participants with bipolar disorder. Although we corrected for age in our analyses, increasing age provides greater opportunities for cognitive and functional skill development, therefore it is possible that the current results are an underestimation of the difficulties adolescents with bipolar disorder have.
4. Discussion The present study examined neurocognition and psychosocial functioning among adolescents with bipolar disorder and was the first study to our knowledge to examine the relationship between neurocognition and functioning in this population. Compared to healthy controls, adolescents with bipolar disorder demonstrated poorer psychosocial functioning in domains of daily activities, social functioning, and satisfaction with their functioning. Adolescents with bipolar disorder also displayed poorer global neurocognition than controls, with the greatest impairment in the domain of visual sustained attention. Contrary to our hypotheses, neurocognition was not a significant predictor of psychosocial functioning; depressive symptoms had the strongest relationships with functioning. In the current sample, we found similar psychosocial functioning impairments as those found in previous reports on adolescents with bipolar disorder (e.g. Goldstein et al. (2009)). We also observed poorer cognitive functioning than healthy controls, similar to results observed in adults with bipolar disorder (Robinson et al., 2006). The differences in cognition were statistically significant for the composite score and for sustained attention, but the level of impairment would be considered to be in the mild range for sustained attention, working memory, and executive functions. Duration of illness and number of mood episodes is associated with cognitive impairment in adult bipolar disorder (Martínez-Arán et al., 2004), making the longitudinal trajectory of cognitive functions as adolescents with bipolar disorder emerge into adulthood, an area in need of attention. We had hypothesized that the relationship between neurocognition and psychosocial functioning would be similar to that observed in adults with bipolar disorder, in which cognitive abilities are consistently found to be the best predictor of functional abilities (Bowie et al., 2010; Depp et al., 2012; Tse et al., 2014). However, in contrast to our hypothesis, neurocognition was not a significant predictor of psychosocial functioning for these adolescents. In fact, depressive symptoms were the only consistent predictor across domains of functioning. It is possible that this relationship was not significant due to the relatively small sample size, though the effect sizes were quite small. An alternative explanation is that at this early stage in the illness, neurocognitive abilities are less impaired and less functionally relevant. For example, there is evidence that bipolar disorder is associated with overachievement during adolescence (MacCabe et al., 2010) despite significantly poorer general intelligence than healthy controls (Vreeker et al., 2016). In addition to academics, we can consider the life demands and our ability to measure functional difficulties fundamentally different in adolescence compared to adulthood. In adulthood, functioning measures tap into skills that are typically performed with independence and with a broader range of consequences. The ecology of adolescents is characterized by structures and consequences imposed by family and school; these may buffer functioning, making neurocognitive ability less directly relevant for functioning during that time period. Symptoms contributing to withdrawal from these structural supports, such as depressive symptoms, may be more relevant for functioning during adolescence, but neurocognitive symptoms may become more important as structural supports diminish in adulthood and responsibility for functioning transitions to a greater extent onto the individual. While neurocognition was not related to psychosocial functioning in this sample, current depressive symptoms were related to daily functioning and satisfaction with functioning. This raises the question of whether neurocognition and functioning are a function of mood state or whether they are stable across mood states. In adults, there is compelling evidence that difficulties persist even in states of euthymia (Martínez-Arán et al., 2004), and there is some evidence that the same is true in adolescent bipolar disorder (Pavuluri et al., 2006). Clinically, depressive symptoms appear to be the most important treatment target to improve psychosocial functioning in adolescent bipolar disorder.
5. Conclusion Adolescents with bipolar disorder demonstrate poorer neurocognitive and psychosocial functioning compared to healthy controls. Contrasting multiple prior studies of adults, neurocognition was not a significant predictor of functioning in this small sample; depressive symptoms were the only consistent predictor across domains of functioning. Treatment of depressive symptoms at this age will be important, but adolescence may also provide an opportunity to enhance neurocognitive abilities necessary for functioning as adolescents emerge into adulthood. More research on the relationship between neurocognition and psychosocial functioning in this age group is necessary, as well as examinations of cognitive enhancement for improving neurocognition in this age group. 410
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