Cognitive, Family, and Quality-of-Life Characteristics of Youth with Depression Associated with Bipolar Disorder

Abstract

Background:

Depression associated with bipolar disorder (BD) is more common compared to mania. Cognitive, family, and quality-of-life (QOL) factors associated with pediatric bipolar depression are understudied. The goal of this study was to evaluate cognitive, family environmental, and QOL characteristics of youth with bipolar depression.

Methods:

Thirty-two youth (12–18 years of age) with BD type I currently depressed were recruited from inpatient and outpatient setting. Subjects were assessed using the Behavior Rating Inventory of Executive Function (BRIEF), the Family Environment Scale (FES), and the Child Health Questionnaire-Parental-Form 50 (CHQ-PF50). Results were compared with population norms and the relationship between these domains was calculated.

Results:

Youth with depression associated with BD did not show significant impairment in executive functions. They displayed impaired family environment in the domains of cohesion, independence, achievement orientation, and organization. Youth also displayed impairments in the psychosocial health domains compared with the population normative data. The CHQ-Psychosocial health significantly negatively correlated with the BRIEF-Global Executive Control score (r = −0.76, p < 0.0001).

Conclusion:

Depression in youth with BD is associated with impairments in family functioning and QOL. Impairments in psychosocial QOL are associated with cognitive functioning. Further intervention studies examining executive functioning and family environment as treatment targets are needed.

ClinicalTrials.gov identifier:NCT00232414

Introduction

Bipolar disorder (BD) is a chronic, severe, and highly disabling psychiatric disorder characterized by recurrent episodes of depression and mania (Grande et al., 2016). Individuals suffering with BD have low life satisfaction, high rates of disability, comorbid medical problems, and suicide attempts or completions (Goldberg and Harrow, 2005; Gomes et al., 2016; Keenan-Miller et al., 2012). Patients with BD usually experience symptom onset before the age of 18 years and early onset is characterized by more severe courses of illness and more functional impairments over time compared to patients with onset after the age 18 years (Perlis et al., 2004).

In youth with early course BD, depressive symptoms and episodes tend to be more prevalent and more persistent than manic episodes and symptoms (Duffy et al., 2019). In addition, studies suggest depression may be more deleterious to youth's psychosocial functioning and quality of life (QOL) (Van Meter et al., 2013). Youth with BD, while depressed, report higher levels of guilt, social withdrawal, appetite changes, rejection sensitivity, and suicidality (Birmaher et al., 2009). Despite this, compared to mania, bipolar depression in youth remains understudied. Understanding the developmental process and pathway involved in the origin and maintenance of psychopathology requires multiple levels of analysis from neurobiological to the individual and to the context in which the individual is embedded.

In youth, three understudied psychopathology domains involved in the adverse outcomes seen in bipolar depression are cognitive deficits, family environment, and health-related quality of life (HRQOL). Neuropsychological and cognitive deficits are highly prevalent in youth with BD (Frias et al., 2014), with deficits in executive functioning being a common finding (Walshaw et al., 2010). Youth with BD and deficits in executive functioning are at a high risk of academic problems (Biederman et al., 2011).

Family environment is repeatedly shown to be affected in families of youth diagnosed with BD, regardless of the mood state (MacPherson et al., 2018). High familial expressed emotion (EE) plays an important role in the course of illness (Miklowitz et al., 2006). Adolescents with BD and high EE are more likely to have persistent mood symptoms of any state over 2 years (Sullivan et al., 2012).

Significantly less warmth, affection, and intimacy and greater conflict and hostility were reported in families with euthymic bipolar children compared to healthy controls (Schenkel et al., 2008). Furthermore, youth with BD who endorsed suicidal ideation reported greater family conflict, rated their family environment as significantly less adaptable, and reported a greater overall number of stressful family events (Goldstein et al., 2009; Weinstein et al., 2015). In addition, manic bipolar youth exposed to low maternal warmth are four times more likely to relapse after recovery compared with those exposed to high maternal warmth (Geller et al., 2008). However, there are limited data regarding the role of family environment in youth in the depressive phase of BD.

HRQOL is significantly impaired both during acute mood episodes and during interepisode periods in adults with BD (IsHak et al., 2012). However, data assessing the impact of BD on the QOL in youth remain sparse (Gomes et al., 2016). Studies in youth with BD reveal that HRQOL is significantly impaired in adolescents in manic or mixed states compared to the national norms (Rademacher et al., 2007). More specifically, psychosocial functioning is typically more impaired than physical functioning (Freeman et al., 2009; Olsen et al., 2012). However, little is known about the HRQOL of depressed youth with BD.

Also, cognitive deficits can lead to problematic behaviors that may negatively affect the family environment. Impairments in cognition and family environment parts of life could ultimately lead to a lower QOL. In fact, bipolar youth have received child- and family-focused cognitive-behavioral therapy to improve both executive and family functioning, which have been associated with overall improvements in bipolar youth's psychosocial functioning (West et al., 2014).

The goal of this study is to explore executive function, family functioning, and HRQOL in youth with BD during a depressive episode. We hypothesized that youth with bipolar depression will have significant impairments in all three domains compared to normative data. In addition, we hypothesized that there would be a significant association between executive functioning impairment and family functioning, which in turn would correlate with HRQOL.

Methods

Participants

Thirty-two adolescents (12–18 years of age) with a depressive episode associated with a previously diagnosed bipolar I disorder were recruited to participate in a treatment study conducted by the Division of Bipolar Disorder Research at the University of Cincinnati and the Pediatric Bipolar Disorder Research Program at Stanford University from March 2006 through June 2007 (DelBello et al., 2009). All study participants were fluent in English, provided written assent, and had a legal guardian who provided written consent before study procedures began.

Patients were excluded for a substance use disorder (other than nicotine) within the previous 3 months; an unstable medical or neurological illness; with antidepressant (other than fluoxetine) and anticonvulsant, antipsychotic or atomoxetine within 3 days; fluoxetine within 4 weeks; or a psychostimulant within 48 hours of baseline. Patients were also excluded if judged to be at risk for suicide (suicidal ideation, intent, or plan, serious attempt within 30 days, or CDRS-R suicide item ≥4 at baseline). Subjects with a prior history of intellectual disability or a diagnosis of autism were also excluded from the study.

The study and all procedures were approved by the institutional review board at the University of Cincinnati and Stanford University. Procedures were conducted in accordance with the International Conference on Harmonization Good Clinical Practice guidelines and with the ethical principles of the Declaration of Helsinki.

Measures

All subjects were evaluated using the Washington University at St. Louis Kiddie Schedule for Affective Disorders and Schizophrenia (WASH-U-KSADS) administered by trained interviewers with established symptom and diagnostic reliability (κ > 0.9) and reviewed by a child and adolescent psychiatrist (Geller et al., 2001). Adolescents and their primary caregivers were interviewed separately, and their responses were combined to ascertain diagnoses. Patients were diagnosed with bipolar I disorder, depressive episode by Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revised (DSM-IV-TR) criteria, and were required to have screening and a baseline CDRS-R score ≥40. In addition to the rating scales used for the measurement of the primary outcome of mood symptoms, three other rating scales were used to assess executive functioning, family environment, and QOL of the subjects.

Executive functioning was assessed using the Behavior Rating Inventory of Executive Function (BRIEF). The BRIEF is a standardized and validated instrument that measures components of executive functioning in youth 5–18 years of age (Gioia et al., 2002). This parent-rated measure contains 86 items and has 8 scales, which in turn comprise 2 indices: A Behavioral Regulation Index (BRI) (inhibit, shift, and emotional control) and a Metacognition Index (MI) (initiate, working memory, plan/organize, organization of materials, and monitor).

These two indices comprise a Global Executive Composite (GEC) score. Raw scale scores are transformed into T-scores for interpretation such that a score of 50 represents the mean for the normative group and 10 points represent 1 standard deviation (SD) from the mean. Higher scores represent greater levels of dysfunction. T-scores at or above 65 are considered clinically significant. The BRIEF has good internal consistency and acceptable test-retest reliability (Donders et al., 2010; Egeland and Fallmyr, 2010; Toplak et al., 2009).

Family functioning was assessed using the Family Environment Scale (FES), a 90-item true false questionnaire (Fowler, 1982). The FES evaluates 10 subscales with three dimensions: the Relationship Dimension (Cohesion, Expressiveness, and Conflict), the Personal Growth dimension (Independence, Achievement Orientation, Intellectual-Cultural Orientation, Active-Recreational Orientation, and Moral-Religious Emphasis), and the System Maintenance dimension (Organization and Control). The Relationship and System Maintenance dimensions reflect internal family functioning, and the Personal Growth dimension reflects the links between the family and the larger social context. Normative FES data are available, composite scores become T-scores to interpret the results. T-scores from 40 to 60 are considered the normal range (Boyd et al., 1997). The FES has good internal consistency, test–retest reliability, and construct and discriminant validity (Loveland-Cherry et al., 1989).

QOL was measures using the Child Health Questionnaire-Parental Form 50 (CHQ-PF50) (McErlain and Gaffney, 1997). The CHQ-PF50 is a multidimensional generic measure HRQOL; it measures 14 domains of physical and psychosocial health. The physical domains analyzed include physical function, role physical, general health perceptions, and bodily pain (BP). Psychosocial domains analyzed include role-emotional-behavioral, parental impact-time, parental impact-emotional, self-esteem, mental health, and behavior (Hepner and Sechrest, 2002). The CHQ-PF50 has undergone extensive validation, and normative data are available (Landgraf et al., 1996). In addition, global functioning was assessed with the Children's Global Assessment Scale (CGAS).

Data analysis

The FES and CHQ-PF50 subscale scores were compared with normative samples using independent two-sample t-tests when normative means and SDs were available. CHQ-PF50 summary scores and BRIEF scores were compared to normative samples using one-sample t-tests. Pairwise Pearson correlations were calculated among the summary measures of the three assessments (i.e., FES-Relationship, FES-Personal Growth, FES-System Maintenance vs. BRIEF-GEC vs. CHQ-PhS and CHQ-PsS). Any significant relationship was further examined for mediation by fitting regression models with and without the mediating variable and performing the Sobel test (Baron and Kenny, 1986). All significance testing was two sided and used alpha <0.05. Analyses were performed using SAS 9.2.

Results

The sample consisted of 32 adolescents (12–18 years of age) with a depressive episode associated with BD, type I. The participants in the study had the following demographics: 22 (69%) were girls and 26 (81%) self-identified as white. Mean age was 15.5 years (SD = 2 years), and mean age at onset of BD was 11.5 years. Three of the 32 adolescents (9%) in the study had psychotic symptoms at baseline. Rates of co-occurring disorders were as follows: four (12%) had ADHD, eight (25%) had anxiety disorders, and eight (25%) had a disruptive behavior disorder.

Twelve outpatients at Stanford University and 5 outpatients and 15 inpatients from the University of Cincinnati were included in the study. Subjects had an average duration of current depressive episode of 6 (SD = 5.3) months and had an average of 2.6 (SD = 2.2) prior depressive episodes. The average CGAS of the sample was 33.3 (SD = 13.2). There was no significant difference in demographics or clinical characteristics between subjects at Stanford University and the University of Cincinnati.

Behavior Rating Inventory of Executive Function

The mean T-scores and 95% confidence intervals (CIs) are shown in Table 1. All scores are significantly greater than the normative mean of 50, as evidenced by the CIs. Although the inhibit, shift, initiate, memory, plan, BRI, MI, and GEC mean T-scores were all above 65, which signifies clinically significant impairment, the 95% CIs have a range that includes values below 65, giving each a nonsignificant p-value. However, there was a trend toward a significant value for the GEC score (p = 0.05).

Table 1.

Means of Behavior Rating Inventory of Executive Function Results of Executive Functioning in Bipolar Depressed Youth (n = 32)

	Mean	SD	95% CI		p
Inhibit	69.2	15.4	63.7	74.8	0.131
Shift	66.9	13.6	62.0	71.8	0.441
Emotional	62.4	7.7	59.6	65.2	0.064
Initiate	66.7	10.8	62.8	70.6	0.376
Memory	67.4	13.8	62.5	72.4	0.324
Plan	66.6	11.1	62.6	70.6	0.422
Organize	58.3	9.1	55.0	61.6	<0.001
Monitor	62.6	10.0	59.0	66.2	0.177
BRI	68.2	11.4	64.1	72.4	0.117
MI	67.4	10.7	63.6	71.3	0.212
GEC	68.7	10.3	64.9	72.4	0.054

BRI, Behavioral Regulation Index; BRIEF, Behavior Rating Inventory of Executive Function; CI, confidence interval; GEC, Global Executive Composite; MI, Metacognition Index; SD, standard deviation.

Family Environment Scale

The FES questionnaire was completed for 31 of 32 adolescents at the baseline visit. Adolescents with bipolar depression had significantly lower scores in 7 out of 10 FES subscales compared to the population means. As shown in Table 2, the most significant impairments were found in the levels of cohesion (p < 0.0001), independence (p < 0.0001), achievement orientation (p < 0.0001), and organization (p = 0.0002). Adolescents with bipolar depression also had lower scores on intellectual-cultural orientation (p = 0.03) and moral-religious (p = 0.02) scales. From the dimensional perspective, adolescents with bipolar depression had the most impairment in subscales of the Personal Growth dimension.

Table 2.

Comparisons of Mean Family Environment Scale Scores of Youth with Bipolar Depression (n = 32) and Population Norms

	BDY, mean	SD	95% CI	Normative, mean	SD	95% CI	t	p
Cohesion	5.52	1.50	4.96–6.07	6.73	1.47	6.65–6.81	−4.5	<0.001
Expressiveness	5.74	1.41	5.22–6.26	5.54	1.61	5.46–5.62	0.7	0.493
Conflict	3.26	1.21	2.81–3.70	3.18	1.91	3.08–3.28	0.4	0.722
Independence	3.42	1.43	2.89–3.94	6.66	1.26	6.59–6.73	−12.5	<0.001
AO	4.16	1.49	3.62–4.71	5.47	1.62	5.39–5.55	−4.5	<0.001
ICO	5.06	1.21	4.62–5.51	5.56	1.82	5.47–5.65	−2.2	0.032
ARO	4.71	1.53	4.15–5.27	5.33	1.96	5.23–5.43	−1.7	0.080
MRE	4.13	1.43	3.60–4.65	4.75	2.03	4.64–4.86	−2.4	0.024
Organization	4.19	1.47	3.65–4.73	5.47	1.9	5.37–5.57	−3.7	<0.001
Control	4.13	2.11	3.36–4.90	4.26	1.84	4.16–4.36	−0.4	0.698

AO, achievement orientation; ARO, active-recreational orientation; BDY, Bipolar depressed youth; CI, confidence interval; FES, Family Environment Scale; ICO, intellectual-cultural orientation; MRE, moral-religious emphasis; SD, standard deviation.

Health-related quality of life

Mean CHQ-PF50 scores for our sample of adolescents with bipolar depression and U.S. population norms appear in Table 3. There was no significant difference in the physical health domains of adolescents with bipolar depression compared to the normative sample, except for BP (p = 0.002). All the domains of psychosocial health were substantially lower (p < 0.0003) in adolescents with bipolar depression compared with the U.S. normative sample. The PhS T-score was not significantly different from the general population mean of 50, while the PsS T-score was significantly lower than 50 (p < 0.0001).

Table 3.

Health-Related Quality of Life in Youth with Bipolar Depression (n = 32) Compared to the Population Norms

CHQ-PF50	BDY, mean	SD	95% CI	United States, mean	SD	95% CI	t	p
PF	92.5	23.3	84.1–100.9	90.9	16.4	89.9–91.9	0.4	0.689
RP	86.5	30.1	75.6–97.3	91.5	18.9	90.3–92.7	−0.9	0.353
GH	71.4	15.4	65.8–77.0	66.7	19.4	65.5–67.9	1.4	0.175
BP	65.3	22.4	57.2–73.4	78.7	20.7	77.4–80.0	−3.3	0.002
REB	60.1	40.7	45.4–74.7	90.4	19.5	89.2–91.6	−4.2	<0.001
PT	61.8	27.1	52.0–71.6	83.9	20.3	82.6–85.2	−4.6	<0.001
PE	38.3	18.8	31.5–45.1	74.0	21.4	72.6–75.4	−9.3	<0.001
SE	41.5	20.8	34.0–49.0	79.3	17.8	78.2–80.4	−11.7	<0.001
MH	41.7	18.6	35.0–48.4	77.3	13.7	76.4–78.2	−10.7	<0.001
BE	42.0	22.0	34.0–49.9	72.3	17.1	71.2–73.4	−7.7	<0.001
Physical T-score	53.0	10.3	49.3–56.7	50.0	10.0		1.6	0.111
Psychosocial T-score	25.1	12.5	20.6–29.6	50.0	10.0		−11.2	<0.001

BDY, bipolar depressed youth; BE, behavior; BP, bodily pain; CHQ-PF50, Child Health Questionnaire-Parental-Form 50; CI, confidence interval; GH, general health perceptions; MH, mental health; PE, parental impact-emotional; PF, physical function; PT, parental impact-time; REB, role emotional-behavioral; RP, role physical; SD, standard deviation; SE, self-esteem.

FES, BRIEF, and CHQ-PF50 associations

The associations between the FES, BRIEF, and CHQ-PF50 summary measures were examined with Pearson correlation coefficients. The CHQ-PsS was significantly negatively correlated with the BRIEF-GEC (r = −0.76, p < 0.0001). There was no other significant correlation. The Sobel test was performed to test if any of the three FES summary scores mediated this relationship. These tests showed no mediating effect of FES-Relationship (p = 0.49), FES-Personal Growth (p = 0.86), or FES-System Maintenance (p = 0.99).

Discussion

In this study we set out to describe the executive function deficits, alterations in family environment, and the HRQOL among adolescents with bipolar depression. In terms of executive function, we saw that overall adolescents with bipolar depression had deficits compared to the normative mean with mean values on the range of clinically significant; however, none reached statistical significance. In this study, we saw that depressed adolescents with BD had significant impairment in subscales of the Personal Growth dimension of the FES scale.

The physical health domains did not significantly differ between depressed bipolar adolescents and the normative sample, but there was significant impairment in all domains of psychosocial health compared to the normative sample. We also identified a significant negative correlation between executive functioning and psychosocial health. The results of our study are consistent with current literature emphasizing the importance of taking a broader approach when defining the magnitude of impairments and the goals of treatment of youth with bipolar depression.

We observed impairment in executive functioning in youth with bipolar depression, as evidenced by the elevated BRIEF scores, although these differences did not reach statistical significance. The affected domains included the ability to shift cognitive set and to modulate emotions and behavior through inhibitory control, and the ability to initiate, plan, organize, and sustain future-oriented problem solving in working memory. In comparison, one of our previous studies using the BRIEF scale on adolescents in a manic or mixed episode found that executive functioning in bipolar patients was significantly more impaired than healthy volunteers (Shear et al., 2002). In that study, we also found more significant impairments in the BRI than the MI. In our sample of subjects, neither BRI nor MI was close to clinical significance, suggesting a difference in executive functioning between the two mood states.

We also saw in our sample an impairment in the family environment. The most significant impairments were found in the areas of interpersonal interactions and personal growth. Interestingly, the conflict scores in our sample did not significantly differ from the normative sample. Previous studies have found high conflict scores in children with BD and their families (Belardinelli et al., 2008; Timmins et al., 2016). One study found that parent-reported family conflict, adaptability, and cohesion were better among families with manic children rather than depressed children, while depressive symptoms were associated with lower ratings of family functioning (Keenan-Miller et al., 2012; Van Meter et al., 2013).

Studies of children with BD or children with family members diagnosed with BD found low cohesion scores and low expressiveness scores, which reflect poor family communication and demonstrate that family members are not encouraged to directly express their feelings (Romero et al., 2005). In our sample, there was significant impairment in the cohesion scores; however, there was no significant impairment found in the expressiveness scores.

All five of the Personal Growth dimension subscales were impaired in our sample. Consistent with our findings, prior studies have found that families of children with BD scored significantly lower on intellectual-cultural orientation and active-recreational orientation (Belardinelli et al., 2008; Romero et al., 2005).

Although family functioning deficits were not associated with HRQOL, treatments aimed at improving family functioning have been associated with improvement in outcome in bipolar youth. Specifically, family-focused therapy, Multi Family Psychoeducation Group, Individual Family Psychoeducation Programs, and other treatment modalities involving family members are effective for treating adolescents with bipolar depression (Frias et al., 2015).

In past studies, family-focused therapy and cognitive-behavioral therapy were found to be more effective for treatment of depressive symptoms than individual psychoeducational and systematic care programs (Miklowitz et al., 2008); however, a more recent study found that family-focused therapy was no better than enhanced care (family psychoeducation) at improving the severity or recovery time of bipolar depression when used in conjunction with pharmacotherapy (Miklowitz et al., 2014). Communication enhancement training may help to improve family cohesion and the impairment in the Personal Growth dimension by improving the quality and efficiency of family interactions (Miklowitz et al., 2004).

There is a paucity of data about the HRQOL in bipolar adolescents. Part of the reason may be that QOL is a very broad construct, covering all major aspects of life. However, QOL is an important measure of the overall functioning of bipolar adolescents in multiple domains. QOL is also important in the assessment of treatment effects on the overall functioning in the context of the family, peers, and school environment. There is some evidence suggesting that psychopharmacological interventions may improve the HRQOL in youth with BD (Olsen et al., 2012). The HRQOL in our sample of adolescents with bipolar depression was significantly impaired compared to the normative sample.

Like prior studies, we observed greater impairment in psychosocial functioning than in physical health. Similar findings were reported in other studies of QOL assessment in bipolar youth with a manic or mixed episode (Olsen et al., 2012; Rademacher et al., 2007). However, recently, bipolar depression in children was associated with poorer physical well-being, self-esteem, and overall QOL than bipolar manic children (Van Meter et al., 2013).

Our hypothesis about the correlations between the family environment, executive functioning, and the QOL impairment was only partially confirmed. We found significant associations between the executive functioning and the psychosocial QOL measure, suggesting that greater impairment in cognitive functioning is associated with lower QOL in this population. Indeed, intact cognitive abilities are necessary to perform daily tasks at an appropriate level. If this process is impaired, the overall QOL might also be impaired. Therefore, improvement of executive functioning may be an important treatment goal to improve the QOL of bipolar depressed youth. Because Goal Management Training has been effective for the rehabilitation of executive functioning following brain injury, this treatment in conjunction with other interventions such as Problem Solving Therapy may be a possible intervention to improve the impairments in executive function and, subsequently, the QOL in bipolar depressed youth (Krasny-Pacini et al., 2014; Passarotti et al., 2019).

Because of multiple comorbidities of bipolar adolescents in this study, the results may not be generalizable to bipolar youth without comorbid disorders. Although this study did not particularly look at the difference between bipolar youth with and without comorbid psychiatric disorders, results from another study found that bipolar youth with an externalizing disorder (including disruptive behavior disorders and ADHD) and/or anxiety disorder exhibit lower family cohesion and higher family conflict than those without comorbidities; comorbidities in youth are associated with worse family functioning (Esposito-Smythers et al., 2006). Another study found that bipolar patients with comorbid ADHD had significantly more impairment in neurocognitive functioning than those with BD alone (Frias et al., 2014).

Conclusions

There are several potential limitations to this study. First, FES and HRQOL data were derived from parent reports, rather than child reports. Second, the number of subjects was small (n = 32), which could potentially lead to low power to detect differences. Third, the multiple comparisons in this study could have led to significant findings where there should not be. This study was composed of only bipolar I disorder patients who typically have more severe episodes than bipolar II patients, and bipolar adolescents in mood states other than depression were not included. This study also excluded individuals with suicidal ideation, which may have led to worse outcomes in all measures.

In fact, youth with BD who present with suicidal ideation describe their family environment as significantly less adaptable and report a greater overall number of stressful family events, compared to those with no suicidal ideation (Goldstein et al., 2009). Also, because this study was a substudy of a treatment study, it excluded subjects with an increased suicidal risk; this may have limited our sample to less severe participants, it is possible that cases with severe depression present different levels of cognitive issues and accompanying problems in family functioning. Finally, we compared all the scores of youth with bipolar depression to population norms, so there is no way to disentangle bipolar depression from BD in general.

Despite these limitations, the results of our study emphasize the importance of conducting a comprehensive assessment of various aspects of the patient's life, in addition to the core mood symptoms. Our findings also suggest treatment of bipolar depression and BD in youth in general needs to focus on multiple outcome measures, including psychoeducation and improvement of family functioning. Indeed, combination of pharmacotherapy and psychotherapy has been shown to reduce the risk (up to 40%) of any type of mood relapse over 1- to 2-year periods relative to comparison conditions and to enhance social functioning (Scott et al., 2007). Future studies using family and executive functioning and HRQOL as primary outcome measures in investigations of depressed bipolar youth are needed.

Clinical Significance

BD is a chronic, severe, and highly disabling mental health disorder that starts in adolescents. Youth with BD will experience more depressive episodes compared to manic episodes. Beyond symptomatic domains, impairments in cognitive and psychosocial functioning are understudied. Depression in youth with BD is associated with impairments in family function and quality of life.

Authors' Contributions

A.D.: Conceptualization (lead), methodology (lead) writing (colead), and analysis. L.R.P.: Methodology (co-lead), analysis (supporting), and writing (colead). T.B., K.D.C., C.M.A., and M.P.D.: Methodology (equal) and reviewing and editing (equal). T.J.B. and J.A.W.: Methodology (equal), reviewing and editing (equal), and conceptualization (equal).

Disclaimer

The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Disclosures

L.R.P. has received research support from Eli Lilly, Pfizer, Otsuka, Novartis, Lundbeck, Sunovion, AbbVie, Martek, and Shire. J.A.W. has received research support from National Institute of Mental Health. C.M.A. has received research support from National Institute of Mental Health, Johnson and Johnson, Merck, Forest, Otsuka, Purdue, Takeda, Pfizer, Shire, Sunovion, and SyneuRx; and has received consulting/honoraria from Sunovion. M.P. D. has received research support from National Institute of Mental Health, National Institute of Child Health and Human Development, Amylin, Eli Lilly, Pfizer, Otsuka, GlaxoSmithKline, Merck, Martek, Novartis, Lundbeck, Pfizer, Sunovion, and Shire; and has received consulting/advisory board/honoraria/travel support from Pfizer, Lundbeck, Sunovian, Supernus, and Otsuka. The other authors have no disclosures. The authors declare no competing interests.