© Borgis - New Medicine 4/2009, s. 104-108
*Ildikó Baji1, 3, Nestor L. Lopez-Duran2, Maria Kovacs2, Charles J. George2, László Mayer3, Krisztina Kapornai3, Enikő Kiss3, Marike Vuga4, Julia Gádoros1, Ágnes Vetró3
The relations of age, sex and symptom characteristics of childhood depression in a Hungarian clinical sample
1Vadaskert Hospital, Budapest, Hungary
Head: Dr Julia Gadoros, PhD
2University of Pittsburgh School of Medicine, Department of Psychiatry, Pittsburgh, Pennsylvania
Head: Prof. Dr Maria Kovacs PhD
3Department of Child and Adolescent Psychiatry, University of Szeged, Szeged, Hungary
Head: Dr Agnes Vetro PhD
4University of Pittsburgh, Department of Public Health, Pittsburgh, Pennsylvania
Head: Dr Maria Kovacs PhD
Summary
Objective.We examined age, sex, and age-by-sex interaction effects in depressive symptoms in a clinical sample of children and adolescents.
Method. The sample included 559 children (247 females) with major depressive disorder (mean age = 11.69 years; range = 7 to 14). Participants were recruited from 23 mental health facilities in Hungary. Symptom rates were obtained via the Interview Schedule for Children and Adolescents – Diagnostic Version (ISCA-D). Final diagnosis was rendered via the best-estimate diagnostic procedure based on DSM-IV diagnostic criteria.
Results. Six symptoms increased with age: depressed mood (OR=1.01 p <.05), hypersomnia (OR=1.17 p <.05), psychomotor retardation (OR=1.11 p <.05), fatigue (OR=1.13 p <.01), thoughts of death (OR=1.11 p <.05), and suicidal ideation (OR=1.18 p <.01). Only psychomotor agitation decreased with age (OR=0.91 p <.05). Three symptoms were less common in males: anhedonia (OR=0.95 p <.05), insomnia (OR=0.96 p <.05), and hypersomnia (OR=0.93 p <.05). Only psychomotor agitation was more common in males (OR=2.24 p <.01). No age-by-sex interactions were noted.
Conclusion. The symptom profile of depression appears to become more neurovegetative as children get older, and girls display more affective and atypical symptoms across all age groups.
A large body of research has shown that children and adolescents can meet diagnostic criteria for major depressive disorder as defined in standard diagnostic manuals (e.g., DSM-IV; see review Birmaher et al.) (1). Questions have remained about the appropriateness of such criteria for younger age groups. Are DSM criteria for major depressive disorder (MDD) able to accommodate age-related differences in the likelihood of particular symptoms, and are there different symptoms with MDD as a function of a child´s age, sex, and age-by-sex interactions?
A small number of studies have examined developmental differences in rates of specific symptoms across depressed children and adolescents. There are some discrepant findings, for example, Ryan et al. (2) reported that, compared to depressed children, adolescents with major depressive disorder were more likely to display hopelessness, hypersomnia, and weight gain/loss, and less likely to display psychomotor agitation. In a similar study, Yorbik et al. (3) found that depressed adolescents displayed significantly higher rates of hopelessness, fatigue, hypersomnia, weight loss, and suicidal thoughts than depressed children. However, Mitchell et al. (4) found hypersomnia to be the only symptom more frequent in depressed adolescents than in depressed children.
Examination of sex differences in child and adolescent depression, for example, Mitchell et al. (4), found no sex differences in rates of various depressive symptoms in a sample of children and adolescents with major depression. Similarly, Roberts et al. (5) failed to find sex differences in symptom presentation in a small community-based sample of adolescents meeting criteria for major depression. For example, Williamson et al.6 found higher rates of weight gain among depressed girls compared to boys. Similarly, Yorbik et al. (3) reported that girls with MDD had higher rates of increased appetite than did boys. Ryan et al. (2), however, failed to find sex differences in weight gain or appetite changes, although they found that pre-adolescent boys experienced more fatigue symptoms than pre-adolescent girls.
Our first aim was to examine developmental differences in depressive symptom presentation using age as a continuous variable. Our second aim was to examine sex differences, as well as sex-by-age effects, in symptomatology. Further, given that there is overlap in some symptoms between depression and other disorders (e.g., ADHD), we examined the effect of co-morbid diagnoses on one depressive symptom: psychomotor agitation.
METHOD
Participants
The sample included 559 children (247 females) who have been enrolled in a study of genetic and psychosocial risk factors for childhood onset depression. The mean age at evaluation was 11.69 years (SD: 2.00 years). Ethnic composition was representative of the ethnic composition of Hungary: 93.9% white, 3.6% gypsy (Roma), 2.3% multiracial, and 0.2% African. Subjects were recruited from 23 mental health facilities across Hungary. Inclusion criteria have been described in detail in previous publications (8, 9).
Measures and Procedures
Enrolment and assessment procedures have been described in detail in previous publications (8, 9). Clinical evaluations were conducted with the semi-structured Interview Schedule for Children and Adolescents – Diagnostic Version (ISCA-D), an extension of the Interview Schedule for Children and Adolescents (ISCA10). Each clinician interviewed the parent and the child separately and rendered an overall severity rating for each symptom. Good inter-rater reliability for symptom ratings has been reported (8, 9). Final diagnoses were rendered by experienced psychiatrists using the best-estimate diagnostic procedure (BED) (11). Only those meeting criteria for major depressive disorder at the time of the evaluation were included in the present analysis. We examined the presence or absence of 15 DSM-IV criterion symptoms from the ISCA-D (see table 1). We used clinicians´ overall ratings and dichotomized them as clinically significant (entered into a given diagnosis) versus subclinical or absent.
Table 1. Unadjusted rates (%) of depressive symptoms across age groups.
| | Age at Interview | Statistic |
| 7 | 8 | 9 | 10 | 11 | 12 | 13 | 14 | c2 (1 d.f.) |
| Sample Size | N= 16 | 46 | 70 | 70 | 91 | 91 | 92 | 83 | |
| Depressed Mood | 63 | 61 | 66 | 69 | 73 | 60 | 73 | 81 | 5.04* |
| Irritability | 75 | 76 | 80 | 83 | 86 | 79 | 73 | 81 | |
| Anhedonia | 38 | 43 | 49 | 40 | 43 | 48 | 51 | 43 | |
| Weight Loss | 25 | 28 | 36 | 26 | 26 | 26 | 30 | 40 | |
| Weight Gain | 6 | 28 | 21 | 26 | 26 | 16 | 24 | 14 | |
| Insomnia | 63 | 46 | 60 | 49 | 63 | 55 | 55 | 57 | |
| Hypersomnia | 13 | 11 | 6 | 10 | 11 | 14 | 17 | 23 | 9.33** |
| Psychomotor Agitation | 63 | 52 | 56 | 53 | 45 | 36 | 39 | 43 | 7.70** |
| Psychomotor Retardation | 31 | 30 | 34 | 29 | 37 | 46 | 39 | 47 | 6.49* |
| Fatigue | 69 | 41 | 60 | 63 | 64 | 70 | 67 | 70 | 7.57** |
| Feelings of Worthlessness | 44 | 50 | 59 | 57 | 59 | 63 | 60 | 63 | |
| Guilt | 25 | 35 | 41 | 33 | 31 | 35 | 30 | 35 | |
| Impaired Decision Making | 75 | 65 | 73 | 76 | 70 | 70 | 67 | 75 | |
| Thoughts of Death | 44 | 35 | 59 | 61 | 55 | 68 | 55 | 65 | 6.69** |
| Suicidal Ideation | 25 | 17 | 34 | 39 | 41 | 44 | 45 | 49 | 13.87*** |
* p <0.05, ** p <0.01, *** p<0.001 Mantel-Haenzel χ2
Statistical Analysis
To estimate the effect of age, sex, and age-by-sex interactions on symptom presentation, we used alternating logistic regression (ALR) (7), fitting a multivariate model of age and sex on the 15 symptoms of interest. ALR is a type of generalized estimating equations (GEE)12 that allows us to simultaneously model the endorsement of each of the 15 symptoms while accounting for the possible inter-correlation of symptoms within participants. This method was initially created for analysis of inter-correlated cluster data (13) and has been extended to the analysis of inter-correlated outcomes (14).
RESULTS
Unadjusted rates of specific depressive symptoms by age and sex
Table 1 presents the rates of endorsement of each symptom by age. Depressed mood, hypersomnia, psychomotor retardation, fatigue, thoughts of death, and suicidal ideation increased linearly with age. Psychomotor agitation was the only symptom that decreased linearly with age. Table 2 presents the rates of endorsement of each symptom by sex. Six symptoms were significantly more common in females than males, namely: depressed mood, anhedonia, insomnia, hypersomnia, psychomotor retardation, and thoughts of death. In contrast, only psychomotor agitation was more commonly reported in males than in females.
Table 2. Unadjusted rates of depressive symptoms for girls and boys.
| Girls (n=247) % | Boys (n=312) % | c2 |
| Depressed Mood | 74.1 | 65.4 | 4.90* |
| Irritability | 77.7 | 81.1 | n.s. |
| Anhedonia | 51.0 | 41.0 | 5.55* |
| Weight Loss | 32.8 | 28.2 | n.s. |
| Weight Gain | 22.3 | 20.8 | n.s. |
| Insomnia | 61.1 | 51.6 | 5.08* |
| Hypersomnia | 18.2 | 9.9 | 8.05** |
| Psychomotor Agitation | 38.5 | 51.6 | 9.59** |
| Psychomotor Retardation | 43.7 | 34.0 | 5.47* |
| Fatigue | 65.6 | 62.8 | n.s. |
| Feelings of Worthlessness | 61.1 | 57.1 | n.s. |
| Guilt | 33.2 | 34.3 | n.s. |
| Impaired Decision Making | 67.2 | 74.4 | n.s. |
| Thoughts of Death | 62.8 | 54.2 | 4.17* |
| Suicidal Ideation | 43.7 | 36.5 | n.s. |
*p<0.05, **p<0.01 n.s. = Not statistically significant at nominal alpha <0.05.
Age and sex effects in rates of depressive symptoms adjusted for inter-correlation between symptoms.
Table 3 shows the adjusted odds ratio of each symptom by sex and age while controlling for age, sex, and the correlation between symptoms. Results from the ALR indicated a significant effect of age χ2(16) = 35.91, p = 0.003 and sex, χ2(16) = 38.65 p = 0.001. No age by sex interaction was observed, χ2(16) = 16.53 p = 0.42. Consistent with the unadjusted results presented above, and while controlling for sex and the inter-correlation between symptoms, the odds ratio of six symptoms increased with age, namely: depressed mood, hypersomnia, psychomotor retardation, fatigue, thoughts of death, and suicidal ideation. Only psychomotor agitation was more frequent in younger children. While controlling for age and inter-correlation between symptoms, being male significantly decreased the odds of three specific symptoms, namely anhedonia, insomnia and hypersomnia, and significantly increased the odds ratio of psychomotor agitation.
Table 3. Odds ratios of each symptom adjusted for age and sex via alternating logistic regression.
| Symptom | Between-Subject by Symptom Effects
Adjusted Multivariate Odds Ratio (95% C.I.) |
| Age (Year) | Sex (Male) |
| Depressed Mood | 1.10 | (1.01, 1.21)* | 0.71 | (0.49, 1.03) |
| Irritability | 0.98 | (0.88, 1.10) | 1.22 | (0.80, 1.86) |
| Anhedonia | 1.01 | (0.93, 1.10) | 0.67 | (0.48, 0.95)* |
| Weight Loss | 1.06 | (0.96, 1.16) | 0.84 | (0.58, 1.22) |
| Weight Gain | 0.94 | (0.85, 1.03) | 0.87 | (0.58, 1.31) |
| Insomnia | 1.00 | (0.92, 1.09) | 0.68 | (0.48, 0.96)* |
| Hypersomnia | 1.17 | (1.02, 1.35)* | 0.56 | (0.34, 0.93)* |
| Psychomotor Agitation | 0.91 | (0.83, 0.99)* | 1.59 | (1.12, 2.24)** |
| Psychomotor Retardation | 1.11 | (1.01, 1.21)* | 0.71 | (0.50, 1.01) |
| Fatigue | 1.13 | (1.03, 1.23)** | 0.97 | (0.68, 1.39) |
| Feelings of Worthlessness | 1.06 | (0.97, 1.15) | 0.88 | (0.62, 1.25) |
| Guilt | 0.99 | (0.90, 1.08) | 1.04 | (0.72, 1.49) |
| Impaired Decision Making | 1.02 | (0.93, 1.12) | 1.43 | (0.99, 2.08) |
| Thoughts of Death | 1.11 | (1.02, 1.22)* | 0.76 | (0.54, 1.08) |
| Suicidal Ideation | 1.18 | (1.08, 1.29)** | 0.86 | (0.61, 1.21) |
* p <0.05, ** p <0.01. No sex-by-age interactions were noted.
We examined the rate of psychomotor agitation in children without co-morbid attention-deficit-hyperactivity disorder (ADHD; N = 449). Consistent with our full sample analysis, we found an age effect on psychomotor agitation (decreasing rates of agitation in older cases) even among children without co-morbid ADHD, χ2(1) = 7.19 p <.01. Finally, also consistent with our full sample analysis, boys were more likely than girls to present psychomotor agitation after controlling for co-morbid ADHD, χ2(1) = 10.13 p <.01.
DISCUSSION
In this study, we examined age and sex differences in rates of depressive symptoms in a uniquely large sample of children and adolescents diagnosed with major depressive disorder. Our large sample allowed for the simultaneous assessment of age and sex effects using ALR, which controls for possible inter-correlations of symptoms within participants, and provides robust, more reliable estimates than methods previously used. Our findings indicate significant sex and age differences in the presentation of several symptoms, but surprisingly, we did not find any age-by-sex interactions.
Our results are consistent with Weiss and Garber´s15 meta-analytic review in which they concluded that depression is not isomorphic in symptomatology or syndrome presentation throughout early development, and consistent with previous studies2-4. We found that several neurovegetative symptoms increased with age, including hypersomnia, psychomotor retardation, and fatigue. This pattern was accompanied by a significant increase in depressed mood, thoughts of death, and suicidal ideation and a reduction in rates of psychomotor agitation. Specifically, our results indicate that the presentation of depression becomes more neurovegetative as children transition from childhood into adolescence. Our findings are also consistent with Carlson and Kashani´s23 conclusions that depressed mood becomes more frequent with age.
With regard to age effects, our findings are not entirely consistent with DSM-IV criteria according to which irritability can substitute for depressed mood as a required symptom16 in childhood. Specifically, depressed mood and irritability were relatively frequent across all ages with more than 60% of patients displaying them. In contrast, anhedonia was relatively infrequent across all age groups, with rates below 50%. This suggests that anhedonia, and not depressed mood, is the least frequent core symptom in depression among children and adolescents, while irritability is significantly more common, occurring often in conjunction with, rather than as a substitute for depressed mood.
We found that psychomotor agitation symptoms decreased significantly across age groups even among children without co-morbid ADHD, suggesting that this reduction is a component of the changing neurovegetative profile during adolescence.
In regards to sex differences, while controlling for age effects and symptom inter-correlation, we found that girls had significantly higher rates of anhedonia, insomnia and hypersomnia, and lower rates of psychomotor agitation. This suggests that females tend to have a more affective (anhedonic) and atypical (hypersomnia) presentation of depression across all developmental periods. Our study was conducted with a clinical research sample that underwent a more comprehensive and controlled assessment process (e.g., duplicate psychiatric interviews, best-estimate consensus diagnoses). It is possible that this resulted in more reliable diagnoses in our sample and less heterogeneity in co-morbid symptoms and diagnoses, which could otherwise mask some of the sex effects we detected.
Finally, we were surprised that we failed to find any age-by-sex interaction in symptom rates. Given our large sample and analytic technique, we are confident that we would have been able to identify subtle interaction effects had they been there.
In conclusion, we observed stable and elevated rates of irritability, which were concurrent with stable and low rates of anhedonia across all age groups. While current DSM-IV criteria indicate that irritability may be a substitute for depressed mood as a required symptom, our findings indicate that irritability should also be considered as a substitute for anhedonia in this population. Our findings also suggest significant sex differences in the presentation of depression, but these differences are stable across development.
Limitations
Study participants were selected for a genetic study of risk factors of childhood onset depression and our sample selection was biased toward families with two or more children. In this article, however, we only included one child from each family. A further limitation is that depressive symptoms were examined as present or absent. This approach could have obscured more nuanced age and sex effects regarding the severity (rather than rate) of specific symptoms. Finally, our sample encompassed different sex distributions across age groups. In younger ages, we had significantly more boys than girls, while in older ages we had significantly more girls than boys.
This study was partially supported by a grant from the National Institute of Mental Health (NIMH) Grant MH056193 (Drs. Baji, Gádoros, Kovacs, Mayer, Kapornai, Kiss, Vetró and Mr. George).
The authors declare no additional financial or other conflict of interest relevant to the subject of this article.
Piśmiennictwo
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