Comparing Symptoms of Major Depression in Youth with Confirmed Versus Suspected Bipolar Disorder

Abstract

Background:

While numerous studies have compared symptoms of major depressive episodes (MDEs) associated with bipolar disorder (BD; i.e., bipolar depression) versus major depressive disorder (MDD; i.e., unipolar depression), little is known about this topic in youth. We compared MDE symptoms in youth with BD with youth with suspected BD who have similar clinical and familial characteristics aside from having BD.

Methods:

MDE symptoms based on Kiddie Schedule for Affective Disorders and Schizophrenia for School Age Children (K-SADS) Depression Rating Scale items for the most severe past episode were compared in youth, ages 13–21 years, with BD (n = 208) versus suspected BD (n = 165). Diagnoses were confirmed via semistructured interviews. Symptoms with between-group differences (p < 0.05) in univariate analyses were evaluated in a multivariate forward stepwise regression. All analyses controlled for age and sex.

Results:

Youth with BD had significantly higher (more severe) ratings on depressed mood (p = 0.001, η ² = 0.05), irritability (p = 0.037, η ² = 0.02), anhedonia (p = 0.004, η ² = 0.04), negative self-image (p < 0.001, η ² = 0.07), hopelessness (p = 0.04, η ² = 0.02), fatigue (p = 0.001, η ² = 0.05), hypersomnia (p = 0.001, η ² = 0.05), suicidal ideation (p = 0.04, η ² = 0.02), and recurrent thoughts of death (p < 0.001, η ² = 0.05). In regression analyses, the only symptom that remained significant in the BD group was depressed mood (p = 0.002).

Conclusions:

These findings demonstrate greater severity of depressive symptoms in youth with BD versus MDD across mood, and cognitive and neurovegetative symptom domains. These differences are especially noteworthy given that the MDD group was highly similar to the BD group, aside from BD diagnosis. Present findings emphasize the need for novel treatment approaches to bipolar depression in youth, and for studies examining potential mechanisms underlying the increased severity of bipolar depression.

Introduction

Bipolar depression in adults has been associated with considerable functional impairment, burden of syndromal and subsyndromal symptoms, and reduced quality of life (Judd et al., 2003; Judd et al., 2002). The longitudinal course of bipolar disorder (BD) is overwhelmingly characterized by depressive symptoms. Adults with BD-I spend 31.9% of the time with threshold or subthreshold depressive symptoms, 9.3% of the time with hypomanic or manic symptoms, and 52.7% of the time asymptomatic, while adults with BD-II spend 50.3% of the time with depressive symptoms, 1.3% with hypomanic or manic symptoms, and 46.1% of the time asymptomatic (Judd et al., 2003; Judd et al., 2002).

Findings from adults indicate that there are potential differences between major depressive episodes (MDEs) associated with BD (bipolar depression) versus major depressive disorder (MDD; i.e., unipolar depression). Bipolar depression is more likely than unipolar depression to be characterized by hypersomnia (vs. early insomnia), hyperphagia, atypical depressive symptoms (e.g., leaden paralysis), psychomotor retardation, psychotic features, pathologic guilt, mood lability, irritability, psychomotor agitation, anxiety, and suicidal ideation (Mitchell et al., 2008; Schaffer et al., 2010). Unipolar depression more commonly has initial insomnia, appetite or weight loss, normal or increased activity levels, and somatic complaints (Mitchell et al., 2008; Schaffer et al., 2010). After a careful assessment has failed to identify a history of mania or hypomania, a probabilistic approach has been proposed based on the presence or absence of these symptoms in distinguishing between bipolar and unipolar depression (Mitchell et al., 2008; Schaffer et al., 2010).

Given that the onset of bipolar depression very commonly occurs during adolescence, this represents a pivotal time to recognize the diagnosis and intervene. However, a challenge in making the diagnosis is that bipolar depression often precedes the onset of hypomania/mania (Mesman et al., 2013). Moreover, little attention has been given to the study of the characteristics that differentiate bipolar depression from unipolar depression in youth. Diler et al. (2017b) compared characteristics of MDE among 30 youth with BD with 59 youth with unipolar depression, measured with the Kiddie Schedule for Affective Disorders and Schizophrenia for School Age Children (K-SADS)-Present Version, and found that youth with bipolar depression had greater mood reactivity, hopelessness, cravings for sweets, social withdrawal, and nonsuicidal self-injury (NSSI). Among these symptoms, more severe NSSI and mood reactivity and lower ratings of aches/pains best discriminated bipolar from unipolar depressed youth.

Diler et al. (2017a) have also examined depressive symptoms in depressed youth comparing 61 youth offspring of parents with BD versus 20 community control offspring who did not have parents with BD. The depressed offspring of parents with BD compared with the depressed offspring from the control group had more severe depression, especially atypical depressive features, compared with youth with control offspring. The present study aims to expand on our understanding of features that differentiate bipolar from unipolar depression in youth. Here we present findings from a relatively large sample of youth referred to a subspecialized clinical research program focused on youth with BD. A recently submitted study compares these two groups in terms of demographic, clinical, and familial characteristics, including mania severity (Goldstein et al., 2023).

In the present study, we compared depressive symptoms from the most severe lifetime MDE among youth with confirmed BD versus suspected BD. Analyzing the most severe episode ensured that we would compare a full MDE and also matched severity of episodes across the life-course, rather than selecting the current episode, which could vary in severity. Given that these two groups of youth are highly similar aside from BD diagnosis, comparing these groups may afford unique insights into the differences between unipolar and bipolar depression in youth.

Methods

Participants

Participants were 373 youth, aged 13–20 years old with BD-I, -II, or Not Otherwise Specified (BD-NOS; akin to Other Specified Bipolar and Related Disorder) or probable BD, or considered to be at high risk for BD because of a family history of BD. Participants were recruited from a subspecialty outpatient clinic at a tertiary academic health sciences center in Toronto, Ontario, established to treat and study youth with BD. The study was approved by the institutional research ethics board and participants and at least one parent/guardian provided written informed consent before study commencement. To evaluate the difference in symptoms of depression between youth with and without BD, the sample, all of whom had a history of at least one MDE, was divided into two groups according to whether they met criteria for BD (n = 208) or only for MDD (n = 165).

Diagnostic interview and symptom ratings

All study interviewers had a bachelor's or a master's degree in a health sciences field and were trained under the supervision of the senior author (B.I.G., a licensed child-youth psychiatrist). The Kiddie Schedule for Affective Disorders and Schizophrenia for School Age Children, Present and Lifetime (K-SADS-PL) version (Kaufman et al., 1997) was used to determine current and lifetime diagnoses, including BD and other psychiatric conditions. Diagnoses were based on information derived from interviews with the youth and their parents, and were based on DSM-IV criteria, as this sample was recruited from 2012 through 2017, and the DSM-5 version of the K-SADS-PL was not available until December 2016. Notably, the changes to depression criteria in DSM-5 were minor: removing the bereavement exclusion and adding mixed features.

The mood sections of the K-SADS-PL were substituted with the extended K-SADS Depression Rating Scale (DRS) (Chambers et al., 1985) and K-SADS Mania Rating Scale (MRS) (Axelson et al., 2003). Note that while not all DRS items are DSM-5 symptoms of an MDE, these items will be referred to as symptoms of depression in this article. Diagnosis of BD-NOS was based on operationalized criteria from the Course and Outcome of Bipolar Illness in Youth (COBY) study for duration of symptoms (minimum 4 hours/d) and number of hypomanic days (minimum 4 in lifetime) (Birmaher et al. 2006), while retaining DSM-5 symptom count requirements (i.e., three symptoms when elation was the primary symptom, four symptoms when irritability was the primary symptom).

Diagnoses were determined using all available information, including youth and parent interviews and any available medical records. Clinical judgment was applied when conflicting information arose. Diagnoses were confirmed by a consensus meeting with a licensed child and youth psychiatrist following completion of the K-SADS-PL interview (B.I.G.).

K-SADS-DRS was also used to score symptom severity for each depression symptom for both current and most severe depressive episodes (Table 1 shows anchors for depression symptom severity ratings). The four-factor Hollingshead Scale (Hollingshead, 1975) was used to determine the socioeconomic status (SES). The Children's Global Assessment Scale (CGAS) was used to score the youth's global functioning over the current period, most severe past, and highest level in the past year (Shaffer et al., 1983). Information on comorbid diagnoses and clinical characteristics (e.g., psychosis, psychotropic, and psychosocial treatment history) was obtained from the K-SADS-PL. Anxiety disorders were combined into one variable, “Any Anxiety Disorder(s),” which included generalized anxiety disorder, social phobia, separation anxiety disorder, agoraphobia, and panic disorder. Substance use disorder (SUD) included alcohol or drug abuse or dependence. Lifetime cigarette smoking was also ascertained via the K-SADS-PL, and computed as a “yes” or “no” variable.

Table 1.

Depression Rating Scale Items and Cutoff Threshold Scores

DRS item	Score range ^a	Cutoff threshold score
(1) Depressed Mood	0–7	4
(2) Irritability and Anger	0–7	4
(3) Excessive or Inappropriate Guilt	0–6	3
(4) Negative Self-Image	0–6	3
(5) Hopelessness, Helplessness, Discouragement, Pessimism	0–6	3
(6) Anhedonia, Lack of Interest, Apathy, Low Motivation, or Boredom	0–6	3
(7) Fatigue, Lack of Energy, Tiredness	0–6	4
(8) Difficulty Concentrating, Inattention, Slowed Thinking	0–6	4
(9) Psychomotor Agitation	0–6	3
(10) Psychomotor Retardation	0–6	3
(11) Insomnia	0–6	3
(12) Hypersomnia	0–6	4
(13) Anorexia	0–6	4
(14) Weight Loss	0–6	3
(15) Increased Appetite	0–6	4
(16) Weight Gain	0–6	3
(17) Suicidal Ideation	0–6	3
(18) Number of discrete suicidal acts since onset of present episode (or up to the last 12 months)	n/a	n/a
(19) Suicidal Acts—Seriousness	0–6	3
(20). Suicidal Acts—Medical Lethality	0–6	3
(21) Recurrent Thoughts of Death	0–6	3

1 = not present; 2 = slight; 3 = mild; 4 = moderate; 5 = severe; 6 = extreme; 7 = very extreme.

Threshold scores were included in the DRS (Chambers et al., 1985; Metcalfe et al., 2016).

DRS, Depression Rating Scale; n/a, not applicable.

A Safety Form, which was prepared for the particular study, was augmented from the K-SADS-PL and used to record any lifetime police contact, lifetime involvement with child protective services, lifetime physical or sexual abuse, as well as any suicidality or NSSI that was not captured during the K-SADS-DRS interview (e.g., occurring outside the context of a depressive interval, such as while intoxicated or situationally dysregulated). The Children's Affective Lability Scale (CALS) was used to assess affect regulation using a youth self-report and parent/guardian-report (Gerson et al., 1996). The Life Problems Inventory self-report assessed dimensional traits of identity confusion, impulsivity, emotion dysregulation, and interpersonal problems (Unpublished Manuscript; Rathus and Miller, 1995). Psychiatric history of first- and second-degree relatives was obtained from the youth and parent(s) through the family history screen (Weissman et al., 2000).

Statistical analyses

SPSS version 27 was used to perform all statistical analyses. Demographic and clinical characteristics were compared between youth with BD and youth without BD using t-tests for continuous variables and chi-squared tests for categorical variables. The primary analysis examined between-group differences (BD vs. without BD) in dimensional scores on each item of the DRS, most severe past (i.e., lifetime) episode, using analysis of covariance (ANCOVA) models, controlling for age and sex. Symptoms that were associated with the BD group at p < 0.05 in univariate analyses were evaluated in a multivariate forward stepwise regression. The threshold for inclusion was set at p < 0.05, and the threshold for exclusion was set at p > 0.1. All analyses controlled for age and sex.

In secondary analyses, between-group differences in dimensional scores on DRS items were analyzed separately for males and females, using ANCOVA models, controlling for age.

For descriptive purposes, secondary analyses also examined between-group differences in categorical depressive symptoms (i.e., comparing between those meeting the K-SADS threshold and those not meeting the threshold and comparing severe vs. not severe). The current analyses are exploratory, as all DRS symptoms were evaluated dimensionally and categorically given the gap in prior findings in this area. As such, correction for multiple comparisons of univariate analyses was not applied.

Results

Demographic and clinical characteristics

Data were analyzed from a total of 373 youth with a history of at least 1 MDE, including 208 participants with BD and 165 participants with MDD who were referred for assessment of BD. The demographic and clinical characteristics of the two groups are reported in Table 2. Overall, the two groups were highly similar in terms of demographics, clinical characteristics such as comorbidity, and family psychiatric history. The BD group was more likely to have had an inpatient hospitalization and to have had an eating disorder or psychosis.

Table 2.

Demographic and Clinical Characteristics Among Youth with Major Depressive Disorder and Bipolar Disorder

	Major depressive disorder (n = 165)	Bipolar disorder (n = 208)	Statistics
	Major depressive disorder (n = 165)	Bipolar disorder (n = 208)	t/χ²	p
Demographics
Age	16.49 ± 1.56	16.89 ± 1.60	−2.45	0.02
Female, n (%)	112 (73.2)	134 (73.6)	0.008	0.93
Race (Caucasian), n (%)	130 (78.8)	167 (80.3)	0.13	0.72
Living with natural parents, n (%)	86 (52.8)	117 (56.5)	0.52	0.47
Clinical characteristics, n (%)
History of physical abuse	15 (10.4)	16 (10.7)	0.005	0.94
History of sexual abuse	10 (7.0)	18 (11.7)	1.91	0.17
Inpatient psychiatric hospitalization	48 (29.1)	93 (44.7)	9.55	0.002
Suicide attempt	31 (21.2)	55 (27.4)	1.71	0.19
Nonsuicidal self-injury	88 (60.3)	128 (63.7)	0.42	0.52
Active suicidal ideation	97 (66.4)	144 (71.6)	1.08	0.30
Contact with police	48 (30.2)	78 (37.5)	2.14	0.14
Smoking	72 (43.6)	101 (48.6)	0.90	0.34
Family history of (hypo)mania	78 (47.3)	95 (45.7)	0.10	0.83
Family history of major depressive episode	136 (82.4)	175 (84.1)	0.19	0.68
Lifetime comorbid diagnoses, n (%)
Anxiety disorder	147 (89.1)	180 (86.5)	0.55	0.46
Eating disorder	28 (17)	58 (27.9)	6.18	0.01
SUD	46 (27.9)	77 (37)	3.48	0.06
ODD	56 (33.9)	68 (32.7)	0.06	0.80
CD	11 (6.7)	14 (6.7)	0.001	0.98
OCD	26 (15.8)	44 (21.2)	1.76	0.19
PTSD	16 (9.7)	23 (11.1)	0.18	0.67
ADHD	63 (38.2)	92 (44.2)	1.39	0.24
Psychosis	10 (6.1)	43 (20.7)	16.12	0.001

Values for all continuous variables are written as mean ± SD, categorical variables are written as n (% within group).

ADHD, attention-deficit/hyperactivity disorder; CD, conduct disorder; OCD, obsessive compulsive disorder; ODD, oppositional defiant disorder; PTSD, posttraumatic stress disorder; SD, standard deviation; SUD, substance use disorder.

Univariate analyses

Table 3 presents between-group differences in depression symptoms during the most severe lifetime episode, including test statistics and p-values for ANCOVAs that covary for age and sex. Relative to MDD youth, BD youth had more severe depressed mood (p = 0.001), irritability (p = 0.04), negative self-image (p < 0.001), hopelessness (p = 0.02), anhedonia (p = 0.04), fatigue (p = 0.001), hypersomnia (p = 0.001), suicidal ideation (p = 0.04), and recurrent thoughts of death (p < 0.001).

Table 3.

Depressive Symptom Severity Mean Scores Between Youth with Major Depressive Disorder and Bipolar Disorder

Symptom	Major depressive disorder (n = 165)	Bipolar disorder (n = 208)	Statistics
Symptom	Major depressive disorder (n = 165)	Bipolar disorder (n = 208)	F	p	Partial η²
Negative self-image	4.33	4.51	9.20	<0.001	0.07
Recurrent thoughts of death	3.28	3.52	6.12	<0.001	0.05
Depressed mood	5.28	5.61	5.87	0.001	0.05
Hypersomnia	3.28	3.71	5.76	0.001	0.05
Fatigue	4.37	4.70	5.73	0.001	0.05
Anhedonia	4.60	4.76	4.50	0.004	0.04
Suicidal ideation	3.11	3.45	2.91	0.04	0.02
Irritability/anger	3.44	3.70	2.87	0.04	0.02
Hopelessness	4.14	4.37	2.79	0.04	0.02
Increased appetite	2.03	1.85	2.49	0.06	0.02
Psychomotor agitation	1.82	2.09	2.33	0.07	0.02
Difficulty concentrating	3.89	4.21	2.28	0.08	0.02
Excessive guilt	3.01	3.13	1.48	0.22	0.01
Weight loss	1.70	1.77	1.44	0.23	0.01
Decreased appetite (anorexia)	2.91	3.03	1.37	0.25	0.01
Psychomotor retardation	2.93	3.16	0.97	0.41	0.008
Weight gain	1.65	1.50	0.97	0.41	0.008
Insomnia	3.07	3.19	0.51	0.68	0.004

p-Values of 0.004 or smaller survive Holms' stepdown post hoc correction for set-wise p < 0.05.

Multivariate analyses

A forward logistic regression was completed, entering symptoms found to be significantly different in the above univariate dimensional analyses, including depressed mood, irritability, negative self-image, hopelessness, anhedonia, fatigue, hypersomnia, suicidal ideation, and recurrent thoughts of death. This analysis controlled for age and sex. In this analysis, depressed mood significantly predicted that youth were more likely to be in the BD group (β = 0.36, standard error = 0.12, χ² = 9.63, p = 0.002). Thus, depressed mood was a predictor of having BD versus not having BD with medium effect size. This model accounted for 6% of the variance (Nagelkerke R ² = 0.06).

Secondary analyses

For males, depressed mood (p = 0.04), guilt (p = 0.04), and hypersomnia (p = 0.001) were more severe in the BD group, whereas anhedonia (p = 0.001) and increased appetite (p = 0.02) were less severe in the BD group. For females, depressed mood (p = 0.05), fatigue (p = 0.001), difficulty concentrating (p = 0.04), hypersomnia (p = 0.04), and suicidal ideation (p = 0.05) were all more severe in the BD group.

In univariate categorical analyses, BD youth were significantly more likely to meet the symptom threshold for psychomotor retardation (46.3% vs. 33.9%, χ² = 7.86, p = 0.006), hypersomnia (31.1% vs. 22.6%, χ² = 4.53, p = 0.04), and anorexia (26.3% vs. 17.6%, χ² = 5.43, p = 0.02). There were no categorical symptoms that were more likely to meet threshold in the MDD group. The depressive symptoms with the greatest difference in severity between groups were compared for the percentage who met the threshold for severe. Hypersomnia (43.7% vs. 29.7%, χ² = 7.66, p = 0.006) and fatigue (61.8% vs. 43.9%, χ² = 11.84, p = 0.001) were both found to be more likely to meet the threshold for being severe in the BD group (Table 4).

Table 4.

Proportion of Participants Meeting Threshold for Severe Symptoms

Symptom	Major depressive disorder (n = 165)	Bipolar disorder (n = 208)	Statistics
Symptom	Major depressive disorder (n = 165)	Bipolar disorder (n = 208)	χ²	p	V
Negative self-image	88 (53.7%)	116 (55.8%)	0.17	0.69	0.02
Recurrent thoughts of death	34 (21.1%)	58 (28.2%)	2.38	0.12	0.08
Depressed mood	131 (79.4%)	178 (85.6%)	2.48	0.12	0.08
Hypersomnia	49 (29.7%)	90 (43.7%)	7.66	0.006	0.14
Fatigue	72 (43.9%)	128 (61.8%)	11.84	0.001	0.18
Anhedonia	96 (58.2%)	129 (62%)	0.57	0.45	0.04

Discussion

In this study, we set out to examine for differences in depression symptoms among youth with BD compared with youth with MDD who were referred, but did not meet the criteria, for BD. The results of the present study demonstrated that youth with, versus without, confirmed BD had significantly more severe depressed mood, irritability, negative self-image, hopelessness, anhedonia, fatigue, hypersomnia, suicidal ideation, and recurrent thoughts of death. The differences were largest for negative self-image, recurrent thoughts of death, depressed mood, hypersomnia, fatigue, and anhedonia, which had medium effect sizes, and therefore could be clinically meaningful differences. Depressed mood remained a significant predictor of MDD versus BD in logistic regression analyses. Among symptoms that did not reach statistical significance, the same trend of greater severity for the BD group was observed. Moreover, none of the depression symptoms was more severe in the MDD group.

Taken together, findings in the primary and secondary analyses consistently indicate a greater severity of bipolar depression compared with unipolar depression in clinically referred youth.

The prior study by Diler et al. (2017b) identified a number of differences between bipolar and unipolar depression that were not identified in the current study, including greater mood reactivity, cravings for sweets, social withdrawal, and NSSI, and less aches and pains in the BD group. In contrast, the current study identified a number of differences that were not identified in the Diler et al. study, including greater negative self-image, recurrent thoughts of death, depressed mood, hypersomnia, fatigue, anhedonia, suicidal ideation, and irritability in the BD group.

There are a number of factors that could contribute to the differences between the current study and the Diler study. Foremost among these is the comparison group. Whereas the Diler study focused on a “pure” MDD group, the current study focused on youth referred for BD, who did not meet the criteria for BD but did have a history of MDD. It is possible that factors leading to referral for BD (e.g., mood lability, impulsivity) may have reduced between-group differences in related domains, such as NSSI. Second, the unipolar depression group in the Diler study was significantly younger than the bipolar depression group, and younger than both groups in the current study. While the Diler study analyses controlled for age, it remains possible that the young age of the unipolar depression group in that study contributes, in part, to the differences between that study and the current study.

Third, the fact that more differences were detected in the current study could be explained by greater statistical power given the larger sample size. Finally, from a measurement perspective, the version of the DRS used in the Diler et al. study included additional items that were not included in the current study (e.g., cravings for sweets). Altogether, one can nonetheless conclude that between-group differences in the larger themes of suicidality/self-injury and atypical depression symptoms emerged in both studies.

In addition to comparing present findings with prior youth findings, it is important to also comment on the potential developmental differences versus adult studies. Present findings of more fatigue, hypersomnia, irritability, and suicidal ideation in bipolar versus unipolar depression align with prior adult studies (Mitchell et al., 2008; Parker et al., 2013; Patella et al., 2019; Schaffer et al., 2010). In contrast, prior adult findings of increased appetite and weight, leaden paralysis, psychomotor retardation, psychotic features, mood lability, and psychomotor agitation in bipolar versus unipolar depression (Leonpacher et al., 2015; Mitchell et al., 2008; Parker et al., 2013; Patella et al., 2019; Schaffer et al., 2010) were not replicated in the current study.

Moreover, current findings of increased negative self-image, depressed mood, anhedonia, and hopelessness in bipolar versus unipolar depression are not common differences in adults (Leonpacher et al., 2015; Mitchell et al., 2008; Parker et al., 2013; Patella et al., 2019; Schaffer et al., 2010). These discrepancies may relate to true developmental differences, but could also be explained by methodologic differences. For examples, the K-SADS-DRS does not assess psychotic symptoms or mood lability.

In secondary analyses examining males and females separately, findings were largely consistent, with most depression symptoms being more severe in the BD group in both males and females. Two additional symptoms reached significance, including guilt for males and difficulty concentrating for females. Contrary to the results of the primary analyses, anhedonia and increased appetite were more severe in the MDD group within males. To our knowledge, this analysis was the first attempt to examine differences in bipolar and unipolar depressive symptoms separately for each sex, and more research is needed to better understand the replicability and significance of these differences.

The current study has a number of strengths, in particular the relatively large sample size and the unique comparison group of youth with suspected BD. The advantage of this comparison group is that it reduces the clinical differences between the groups, optimizing the extent to which between-group differences truly reflect differences between bipolar and unipolar depression. The study also has several limitations. First, while the differences were highly significant statistically, the numerical differences were small, which could be difficult to use these findings to discern between these groups clinically. Second, the cross-sectional, retrospective design focuses on symptoms from the lifetime most severe episode of depression. Present findings of between-group differences may not extend to milder depressive intervals.

Third, given the limited literature on this topic, we evaluated multiple variables in an exploratory manner. While the multiple comparisons increase the likelihood of type I errors, the current study provides direction for future hypothesis-driven studies. Fourth, a proportion of the non-BD participants may go on to develop BD. Given the cross-sectional design, we were not able to evaluate whether specific depression symptoms or overall depression severity predicts transition to BD.

Unfortunately, despite the ongoing recognition of the burden of bipolar depression, there remain few evidence-based treatment options that have been studied in youth. Lurasidone and the combination of olanzapine/fluoxetine have been shown to be efficacious for youth bipolar depression in randomized controlled trials (RCTs) (DelBello et al., 2017; Detke et al., 2014), although there have been open studies of lithium and lamotrigine (Chang et al., 2006; Patel et al., 2006). Quetiapine, a mainstay treatment for adult bipolar depression, is of uncertain benefit for youth bipolar depression, although additional studies are needed to address the methodologic limitations of these studies (Goldstein et al., 2017; Yatham et al., 2018).

Three manualized psychotherapy treatments that incorporate family-focused psychoeducation, cognitive behavioral therapy, and communication and problem solving training, as well as dialectical behavior therapy have been found to be efficacious in RCTs for youth BD with improvement in depressive symptoms (Brickman and Fristad, 2022; Goldstein et al., 2024).

Conclusion

Overall, the present study adds to a sparse literature regarding bipolar versus unipolar depression, and incorporates the novel comparison group of youth with MDD who were referred for BD. Current findings demonstrate a consistent pattern of depression symptoms being more severe in those youth with BD. These differences in depressive symptoms spanned multiple symptom domains, including mood, cognitive, neurovegetative, and suicidal ideation. Present findings largely aligned with prior studies of unipolar versus bipolar depression in adults. Given that the non-BD comparison group was complex, with high rates of comorbidity and family psychiatric history, the finding that bipolar depression was more severe than unipolar depression is striking. As such, present findings add further impetus to identify novel prevention and treatment approaches to mitigate the burden of bipolar depression in youth, ideally informed by individual characteristics.

Clinical Significance

Our study showed that youth with depression who have BD have a pattern of more severe depressive symptoms than those with unipolar depression. Thus, the risk of BD in youth with greater depression severity should be carefully considered.

Footnotes

Disclosures

The authors report no disclosures.

Acknowledgments

Preliminary findings from this study were presented at the 25th Annual Conference of the International Society for Bipolar Disorders, held at the Hyatt Regency, Chicago, IL (2023) and the American Academy of Child and Adolescent Psychiatry/Canadian Academy of Child and Adolescent Psychiatry Annual Meeting, held at the Metro Toronto Convention Centre, Toronto, Ontario, Canada (2022). The authors would like to thank all the participants, their families, and the staff at the Centre for Youth Bipolar Disorder.

Study data were collected and managed using Research Electronic Data Capture (REDCap) electronic data capture tools hosted at the Centre for Addiction and Mental Health. REDCap is a secure, web-based software platform designed to support data capture for research studies, providing (1) an intuitive interface for validated data capture; (2) audit trails for tracking data manipulation and export procedures; (3) automated export procedures for seamless data downloads to common statistical packages; and (4) procedures for data integration and interoperability with external sources (Harris et al., 2019; Harris et al., ).

Authors' Contributions

A.M.S.: conceptualization and writing—original draft; M.K.D.: conceptualization, formal analysis, methodology, and writing—review and editing; J.S.B.: formal analysis and writing—review and editing; E.A.Y.: statistics and writing—review and editing; B.I.G.: conceptualization, methodology, writing—review and editing, and supervision.

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