Background
It is well known that assessing previous incidents of hypomania requires special attention and caution in psychiatric practice [
1]. Individuals do not always perceive hypomania as pathological, and as such do not spontaneously report it to clinicians [
2]. Therefore, the recognition of hypomania is frequently delayed, distorting the accurate identification of diagnosis [
3]. Individuals with bipolar disorder (BD) often report that the illness manifested itself early in their life, but accurate diagnosis lagged by many years [
4]. Failure to diagnose or misdiagnosis in BD is a significant clinical and public health problem, as it brings about delayed intervention and an unfavorable treatment outcome.
The need to improve the recognition and diagnosis of hypomania has led to the development of self-report questionnaires for bipolar disorder, including the Mood Disorder Questionnaire (MDQ) [
5], and the Hypomania Checklist (HCL-32) [
6]. The HCL-32 is a self-report questionnaire developed to identify hypomanic components in patients with major depressive episodes [
6]. It has been used as a screening instrument for BDs and bipolar spectrum disorders in various psychiatric clinical settings [
7]. The HCL-32 showed an adequate discrimination power for distinguishing individuals with BDs from those with major depressive disorders in previous studies [
6‐
9]. Those studies also identified two or three sub-domains of the scale representing separate clinical factors. Compared to the MDQ, the HCL-32 showed higher sensitivity and lower specificity in screening hypomania, having high accuracy for the detection of ‘softer’ BD cases [
10]. However, both questionnaires were developed for and have been applied to patients in a depressive episode.
Even though a manic/hypomanic episode is usually preceded by one or more depressive episodes, the polarity of the first episode of illness in BDs is manic (or hypomanic) in at least one third of patients [
11,
12]. Untreated hypomania may be associated with marital, financial, legal, occupational and other psychosocial problems [
13]. Therefore, screening previous and current hypomanic symptoms in individuals without any clear depressive episode would also be important for early detection and adequate treatment of BDs.
The aim of the current study was to test the clinical utility of the HCL-32 for the screening of BDs in the non-clinical adult population. Considering that bipolar I disorder (BD1) and bipolar II disorder (BD2) might have somewhat discrete clinical natures, and that the development of the HCL-32 was originally more focused on BD2 than BD1 [
6], the same analyses were performed separately for these two diagnoses. Additionally, we analyzed both total score and sub-domain scores of the HCL-32.
Results
The demographic and clinical characteristics of the subjects are presented in Table
1. There was no significant difference in age and sex among subject groups. Educational level was significantly higher in the control group compared to patient group (
P < 0.001).
Table 1
Sociodemographic and clinical characteristics of the subjects (n = 533)
Age, years (mean ± SD) | 33.5 ± 9.2 | 33.9 ± 1.3 | 35.0 ± 1.3 | 0.0734 | 0.481 | |
Sex | | | | 3.766 | 0.15 | |
Male | 122 (39.0 %) | 39 (34.8 %) | 31 (28.7 %) | | | |
Female | 191 (61.0 %) | 73 (65.2 %) | 77 (71.3 %) | | | |
Education, n (%) | | | | 36.162 | <0.001 | Control > BD1, BD2 |
College graduate or more | 254 (81.1 %) | 65 (58.6 %) | 61 (56.6 %) | | | |
Hypomania scores (mean ± SD) |
HCL-32 total | 14.7 ± 5.4 | 16.1 ± 6.7 | 17.6 ± 6.5 | 10.527 | <0.001 | BD2 > Control |
Active/elated | 12.4 ± 4.7 | 11.9 ± 5.0 | 13.0 ± 4.9 | 1.401 | 0.247 | |
Irritable/risk-taking | 2.2 ± 1.8 | 3.9 ± 3.0 | 4.5 ± 2.8 | 49.280 | <0.001 | BD2, BD1 > Control |
Patient groups showed higher HCL-32 total score compared to the control group. However, a statistically significant difference was observed only between the BD2 group and the control group (
P < 0.001). For the active/elated factor score, there was no significant difference among subject groups (
P = 0.307). Irritable/risk-taking score was highest in the BD2 group and there was a significant difference among groups (
P < 0.001, control < BD1 < BD2). The positive response rate of each item is presented in Table
2. Ten of 12 items (83.3 %) of the “irritable/risk-taking” factor showed a higher positive response rate in patient groups compared to the control group. Among the 19 items of active/elated factor, 13 items (68.4 %) showed no group difference, and 3 items revealed a significantly higher positive response rate in the control group compared to BD1.
Table 2
Comparison of positive response rate of HCL-32 items among the subjects groups
Active/elated factor
|
1 | need less sleep | 53.0 | 53.6 | 63.0 | 3.344 | 0.188 | 0.27 | |
2 | more energetic | 79.6 | 75.9 | 84.3 | 2.398 | 0.301 | 0.42 | |
3 | more self-confident | 77.9 | 78.6 | 77.8 | 0.027 | 0.987 | 0.97 | |
4 | enjoy my work more | 78.6 | 73.2 | 77.8 | 1.378 | 0.502 | 0.61 | |
5 | more sociable | 70.6 | 67.9 | 70.4 | 0.307 | 0.858 | 0.93 | |
6 | want to travel more | 59.7 | 43.8 | 49.1 | 9.947 | 0.007 | 0.02 | Control > BD1 |
10 | physically more active | 52.9 | 48.6 | 55.1 | 0.977 | 0.613 | 0.69 | |
11 | plan more activities | 77.6 | 64.3 | 83.3 | 12.064 | 0.002 | 0.01 | BD2, Control > BD1 |
12 | have more ideas/creative | 65.5 | 72.3 | 67.6 | 1.752 | 0.417 | 0.53 | |
13 | less shy | 62.3 | 70.4 | 70.1 | 3.552 | 0.169 | 0.26 | |
14 | wear more extravagant clothes | 37.4 | 41.4 | 54.2 | 9.292 | 0.01 | 0.02 | BD2 > Control |
15 | meet more people | 61.9 | 57.7 | 57.0 | 1.102 | 0.576 | 0.67 | |
16 | more interested in sex | 30.8 | 34.8 | 45.8 | 7.945 | 0.019 | 0.04 | BD2 > Control |
18 | talk more | 64.9 | 71.4 | 79.4 | 8.291 | 0.016 | 0.03 | BD2 > Control |
19 | think faster | 66.1 | 65.8 | 73.1 | 1.988 | 0.37 | 0.49 | |
20 | make more jokes | 73.8 | 60.4 | 70.4 | 7.091 | 0.029 | 0.05 | |
22 | engage in more new things | 77.6 | 75.9 | 75.9 | 0.199 | 0.905 | 0.95 | |
24 | do more quickly/easily | 68.4 | 68.5 | 69.4 | 0.044 | 0.978 | 0.97 | |
28 | mood higher, more optimistic | 80.8 | 67.6 | 71.3 | 9.672 | 0.008 | 0.02 | Control > BD1 |
Irritable/risk-taking factor
|
7 | drive faster | 10.0 | 21.6 | 27.9 | 21.993 | <0.001 | <0.01 | BD1, BD2 > Control |
8 | spend more | 39.3 | 48.2 | 61.1 | 15.796 | <0.001 | <0.01 | BD2 > Control |
9 | take more risks | 9.3 | 25.9 | 34.6 | 41.081 | <0.001 | <0.01 | BD1, BD2 > Control |
21 | more easily distracted | 29.7 | 40.2 | 48.6 | 13.619 | 0.001 | <0.01 | BD2 > Control |
23 | thoughts jump | 45.4 | 60.7 | 65.4 | 16.58 | <0.001 | <0.01 | BD1, BD2 > Control |
25 | more impatient/irritable | 14.7 | 44.1 | 40.2 | 50.986 | <0.001 | <0.01 | BD1, BD2 > Control |
26 | can be exhausting or irritating | 5.1 | 32.4 | 27.1 | 61.865 | <0.001 | <0.01 | BD1, BD2 > Control |
27 | get into more quarrels | 2.9 | 24.3 | 23.4 | 55.664 | <0.001 | <0.01 | BD1, BD2 > Control |
29 | drink more coffee | 30.7 | 31.5 | 41.1 | 4.07 | 0.131 | 0.21 | |
30 | smoke more cigarettes | 5.8 | 22.7 | 23.8 | 34.864 | <0.001 | <0.01 | BD1, BD2 > Control |
31 | drink more alcohol | 23.0 | 22.5 | 33.0 | 4.673 | 0.097 | 0.16 | |
32 | take more drugs | 0.6 | 24.1 | 14.2 | 65.772 | <0.001 | <0.01 | BD1, BD2 > Control |
The AUC of the ROC curve and optimal cut-off scores of the HCL-32 and 2 sub-domains for discriminating patients groups from the control group are summarized in Table
3. The AUC range was between 0.51 and 0.75. An AUC of 0.7 or higher was observed only in the irritable/risk-taking factor for discriminating BD and BD2 from the control group. The specificity and sensitivity for screening BD at the optimal cut-off score are also presented in Table
3. The HCL-32 total score showed high specificity (0.82–0.93) and poor sensitivity (0.31–0.36). The irritable/risk-taking factor score had acceptable ranges of specificity (0.62) and sensitivity (0.65–0.74).
Table 3
Analyses of the discrimination power of HCL-32 and its sub-domains in screening BDs
BD1 vs Control |
AUC (95 % CI) | 0.56 (0.51–0.61) | 0.52 (0.47–0.57) | 0.67 (0.62–0.72) |
optimal cut-off score | >19 | ≥12 | >2 |
PPV (%) | 38.87 (28.89–49.60) | 29.72 (23.42–36.65) | 37.96 (31.07–45.24) |
NPV (%) | 77.72 (72.22–81.52) | 76.53 (70.50–81.86) | 83.20 (77.77–87.76) |
sensitivity (95 % CI) | 0.32 (0.24–0.42) | 0.52 (0.42–0.62) | 0.65 (0.55–0.74) |
specificity (95 % CI) | 0.82 (0.77–0.86) | 0.56 (0.50–0.62) | 0.62 (0.56–0.67) |
BD2 vs Control |
AUC | 0.64 (0.60–0.69) | 0.54 (0.49–0.59) | 0.75 (0.70–0.79) |
optimal cut-off score | >21 | >11 | >2 |
PPV (%) | 53.84 (43.54–71.23) | 27.20 (22.06–32.84) | 37.63 (30.82–44.81) |
NPV (%) | 81.31 (76.95–85.17) | 83.27 (76.12–88.99) | 88.50 (83.60–92.36) |
sensitivity (95 % CI) | 0.31 (0.22–0.40) | 0.76 (0.66–0.83) | 0.74 (0.64–0.82) |
specificity (95 % CI) | 0.93 (0.90–0.96) | 0.37 (0.32–0.43) | 0.62 (0.56–0.67) |
BDs vs Control |
AUC | 0.60 (0.56–0.65) | 0.51 (0.47–0.56) | 0.71 (0.67–0.75) |
optimal cut-off score | >19 | >10 | >2 |
PPV (%) | 58.44 (49.66–66.83) | 43.31 (38.28–48.46) | 56.07 (49.94–62.07) |
NPV (%) | 64.57 (59.65–69.28) | 63.82 (55.64–71.45) | 73.99 (68.24–79.19) |
sensitivity (95 % CI) | 0.36 (0.30–0.43) | 0.75 (0.68–0.80) | 0.69 (0.62–0.75) |
specificity (95 % CI) | 0.82 (0.77–0.86) | 0.31 (0.26–0.37) | 0.62 (0.56–0.67) |
Discussion
This study investigated the clinical utility of the HCL-32 for screening BDs in the non-clinical general population. The HCL-32 total score and active/elated factor score did not have adequate screening properties to differentiate patient groups from the control group. However, the irritable/risk-taking factor score with an AUC range of 0.67–0.75 was better able to differentiate between the two groups.
Demographically, female dominance was observed in both the patient group and the control group and had no significant difference among groups. According to a systematic review of prevalence studies, the mean prevalence rate of BDs for males and females was 0.625 % (SD: 0.679) and 0.968 % (SD: 0.945), respectively [
27]. Another review of the prevalence of BDs in general primary care samples also reported higher prevalence in females [
28]. Female dominance has been observed frequently in clinical studies that recruited consecutive cases of BD patients [
29,
30]. Regarding education, the control group was biased to higher educational level, which might affect the positive response rate of their previous mood experiences.
The scores for the patients groups in the current study (16.1 for BD1, and 17.6 for BD2) were similar to those of the initial report of Angst et al. [
6] (18.2 for BD1, and 17.3 for BD2) and other previous studies, i.e., 15.4–18.8 for BD1, and 17.3–18.1 for BD2 [
9,
21]. The mean HCL-32 total score of the control group in the current study (14.7) was similar to those of previous studies, i.e., 15.8 [
31] and 15.7 [
19]. However, the HCL-32 total score of the control group was higher than that of depression patients in previous studies, i.e., 7.9–14.5 [
6,
8,
9,
32,
33]. As a result, the cut-off scores of the HCL-32 yielding the best combination of sensitivity and specificity for screening BDs in the present study (19–21) were higher than the cut-off score of 14 that has been accepted as optimal for discriminating BDs from MDD in previous studies [
6,
8,
32,
34]. In analyzing individual items, high HCL-32 total scores of the control group resulted from a high positive response rate (30.8 % ~ 80.8 %) to items of active/elated factor. This result might indicate that normal persons are more likely to report their experience of positive or high mood state than depressive patients.
The majority of items of irritable/risk-taking factor showed a higher response rate in patient groups in contrast to non-specific high positive response to items of active/elated factor. This phenomenon is indicated by the much better discrimination properties (AUC and sensitivity and specificity at optimal cut-off score) of the risk-taking/irritable factor score compared to the HCL-total score and active/elated factor score. These results are consistent with results of a previous study by Meyer et al. in which German people with probable episodes of hypomania showed a higher score only in the ‘risk-taking/irritable’ factor (not in the ‘active/elated’ factor) compared to the non-hypomanic group [
19]. Other studies also indicated that irritable/risk-taking symptoms might have more relevance to bipolarity and related psychopathological conditions [
19,
31]. In a study of an adolescent group, ‘irritable/erratic’ factor and ‘disinhibited/stimulation-seeking’ factor of the HCL-32 were significantly associated with behavioral and cognitive problems that are prevalent in BDs, while ‘active/elated’ factor negatively correlated with peer problems [
31]. Participants in another adult study cohort reporting irritable/risk-taking hypomania had more depressive symptoms, sleep disturbances, somatic complaints, perceived stress, and lower self-efficacy compared to those reporting active/elated hypomania or no hypomania [
35].
We applied the same analyses in the present study to BD and two subgroups (BD1 and BD2). The HCL-32 total and sub-domains scores showed better discrimination ability in BD2 compared to BDs and BD1. Previous manic episodes are much easier to detect than hypomanic episodes in patients with depressive episodes [
34]. Therefore, the HCL-32 was developed to focus on the identification of hidden hypomanic components in patients with depressive episodes in order to obtain reliable diagnoses of BD2 and bipolar spectrum disorders [
15]. The validity of the HCL-32 in the detection of BD2 and minor BDs in patients with depressive episodes was demonstrated in subsequent studies [
6,
34]. The present study shows that most of the items of irritable/risk-taking factor of the HCL-32 could be useful in the screening of hypomanic state of the BD2 in the non-clinical population.
There are certain limitations to be considered in the interpretation of the present results. First, psychiatric assessments using the structured clinical interview were not performed for the control group which could lead to inclusion of un-diagnosed BD patients in the control group. Second, as patients were recruited in a single psychiatric unit, they could not represent BD patients in general in terms of demographic and clinical characteristics. Third, the current mood state of the patients could have yielded a recall bias on their previous hypomanic state assessed in the HCL-32. Last, differences in the education level between the patients and control groups could be an uncontrolled confounding factor.
Within the mentioned limitations, the present study is meaningful as the first study to evaluate the clinical utility of HCL-32 for screening BDs in non-clinical samples. Our findings indicated that even though the HCL-32 total score and active/elated factor score could not adequately screen BDs from the general population, irritable/risk-taking sub-domain could be clinically useful for distinguishing BDs from the control groups. Beyond its quality as a screening instrument, future studies would be required to explore whether the irritable/risk-taking sub-domain of the HCL-32 might also be useful in assessing the severity measures of the illness in the course of BD.
Competing interests
The authors declare that they have no competing interests.
Authors’ contributions
KL and KSH contributed for the design of the study, interpretation of the results, and preparation of the manuscript. E-HL, J-HK, and KSH coordinated the data acquisition. KL J-HK and KSH wrote the draft manuscript. KL, HO, E-HL, JHK, J-HK, and KSH contributed to the critical revision of article for important intellectual content. All authors read and approved the final manuscript.